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Belete GT, Zhou L, Li KK, So PK, Do CW, Lam TC. Metabolomics studies in common multifactorial eye disorders: a review of biomarker discovery for age-related macular degeneration, glaucoma, diabetic retinopathy and myopia. Front Mol Biosci 2024; 11:1403844. [PMID: 39193222 PMCID: PMC11347317 DOI: 10.3389/fmolb.2024.1403844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 07/24/2024] [Indexed: 08/29/2024] Open
Abstract
Introduction Multifactorial Eye disorders are a significant public health concern and have a huge impact on quality of life. The pathophysiological mechanisms underlying these eye disorders were not completely understood since functional and low-throughput biological tests were used. By identifying biomarkers linked to eye disorders, metabolomics enables early identification, tracking of the course of the disease, and personalized treatment. Methods The electronic databases of PubMed, Scopus, PsycINFO, and Web of Science were searched for research related to Age-Related macular degeneration (AMD), glaucoma, myopia, and diabetic retinopathy (DR). The search was conducted in August 2023. The number of cases and controls, the study's design, the analytical methods used, and the results of the metabolomics analysis were all extracted. Using the QUADOMICS tool, the quality of the studies included was evaluated, and metabolic pathways were examined for distinct metabolic profiles. We used MetaboAnalyst 5.0 to undertake pathway analysis of differential metabolites. Results Metabolomics studies included in this review consisted of 36 human studies (5 Age-related macular degeneration, 10 Glaucoma, 13 Diabetic retinopathy, and 8 Myopia). The most networked metabolites in AMD include glycine and adenosine monophosphate, while methionine, lysine, alanine, glyoxylic acid, and cysteine were identified in glaucoma. Furthermore, in myopia, glycerol, glutamic acid, pyruvic acid, glycine, cysteine, and oxoglutaric acid constituted significant metabolites, while glycerol, glutamic acid, lysine, citric acid, alanine, and serotonin are highly networked metabolites in cases of diabetic retinopathy. The common top metabolic pathways significantly enriched and associated with AMD, glaucoma, DR, and myopia were arginine and proline metabolism, methionine metabolism, glycine and serine metabolism, urea cycle metabolism, and purine metabolism. Conclusion This review recapitulates potential metabolic biomarkers, networks and pathways in AMD, glaucoma, DR, and myopia, providing new clues to elucidate disease mechanisms and therapeutic targets. The emergence of advanced metabolomics techniques has significantly enhanced the capability of metabolic profiling and provides novel perspectives on the metabolism and underlying pathogenesis of these multifactorial eye conditions. The advancement of metabolomics is anticipated to foster a deeper comprehension of disease etiology, facilitate the identification of novel therapeutic targets, and usher in an era of personalized medicine in eye research.
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Affiliation(s)
- Gizachew Tilahun Belete
- Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
| | - Lei Zhou
- Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
- Research Centre for SHARP Vision (RCSV), The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
- Centre for Eye and Vision Research (CEVR), The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
- Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
| | - King-Kit Li
- Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
| | - Pui-Kin So
- University Research Facility in Life Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
| | - Chi-Wai Do
- Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
- Research Centre for SHARP Vision (RCSV), The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
- Centre for Eye and Vision Research (CEVR), The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
- Research Centre for Chinese Medicine Innovation (RCMI), The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
| | - Thomas Chuen Lam
- Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
- Research Centre for SHARP Vision (RCSV), The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
- Centre for Eye and Vision Research (CEVR), The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
- Research Centre for Chinese Medicine Innovation (RCMI), The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China
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Merle BM, Schweitzer C, Rougier MB, Cougnard-Grégoire A, Gayraud L, Delyfer MN, Korobelnik JF, Delcourt C. Associations of circulating vitamins with 10-year retinal neurodegeneration: the Alienor Study. J Nutr Health Aging 2024; 28:100286. [PMID: 38861880 DOI: 10.1016/j.jnha.2024.100286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 05/31/2024] [Accepted: 06/01/2024] [Indexed: 06/13/2024]
Abstract
OBJECTIVE To investigate the associations between circulating vitamins A, D, E, B6, B9, B12 and longitudinal changes in retinal nerve fiber layer (RNFL) thickness. METHODS The Alienor study, a prospective population-based cohort (Bordeaux, France), includes 963 individuals aged 73 years or older at baseline. The present study included 646 participants with complete RNFL measurement and vitamins. Study period is from 2009 to 2020. Peripapillary RNFL thickness was measured using spectral domain optical coherence tomography (SD-OCT). Plasma vitamins A, D and E and, serum vitamins B6, B9 and B12 were measured from blood sample. We performed linear mixed models, adjusted for age, gender, axial length, family history of glaucoma, and alcohol consumption to evaluated associations between vitamins and RNFL thickness changes over time. RESULTS Individuals having higher concentrations of vitamin E, D and B9 had a slower RNFL thinning during the 10-years of follow-up. Indeed, a 1-standard deviation (SD) increase of vitamin E (10.8 μmol/L), D (17.6 nmol/L) and B9 (11 μmol/L) were associated with slower RNFL thinning by 0.14 μm/year (95% confidence interval (CI), 0.03-0.25, p = 0.01), 0.14 μm/year (95% CI, 0.02-0.27, p = 0.02) and 0.11 μm/year (95% CI: 0.007-0.21, p = 0.04), respectively. No significant associations were observed for vitamins A, B6 and B12 with RNFL thinning. CONCLUSIONS Higher levels of vitamins E, D and B9 were associated with a slower RNFL thickness on SD-OCT over time, suggesting that those vitamins may contribute to the neuroprotection of the retina.
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Affiliation(s)
| | - Cédric Schweitzer
- Univ. Bordeaux, INSERM, BPH, U1219, Bordeaux, France; CHU de Bordeaux, Service d'Ophtalmologie, Bordeaux, France
| | | | | | - Laure Gayraud
- Univ. Bordeaux, INSERM, BPH, U1219, Bordeaux, France
| | - Marie-Noëlle Delyfer
- Univ. Bordeaux, INSERM, BPH, U1219, Bordeaux, France; CHU de Bordeaux, Service d'Ophtalmologie, Bordeaux, France
| | - Jean-François Korobelnik
- Univ. Bordeaux, INSERM, BPH, U1219, Bordeaux, France; CHU de Bordeaux, Service d'Ophtalmologie, Bordeaux, France
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Bora RR, Prasad R, Mathurkar S, Bhojwani K, Prasad A. Cardiovascular Manifestations of Pseudoexfoliation Syndrome: A Narrative Review. Cureus 2024; 16:e51492. [PMID: 38304644 PMCID: PMC10831210 DOI: 10.7759/cureus.51492] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Accepted: 01/01/2024] [Indexed: 02/03/2024] Open
Abstract
Pseudoexfoliation syndrome (PEX) is a long-term, age-related extracellular matrix condition that causes aberrant fibrillary pseudoexfoliative material (PXM) to accumulate in various body tissues. The anterior portion of the eye is where this disorder most frequently presents. It affects the entire body. Most frequently, it is seen in older people, usually those over 50. Fibrillar deposits are a symptom of the pseudoexfoliation syndrome and are found in the anterior part of the eye. Deposition of fibrillary white flaky material is seen. The lens capsule, cornea, ciliary epithelium, lens epithelium, iris pigment epithelium, zonules, orbital soft tissues, trabecular meshwork, iris blood vessels, and iris stroma have all been reported to show such depositions. The skin, heart, lungs, liver, kidneys, and other organs have also been reported to contain these deposits. Asymmetrical and bilateral illnesses are both possible. Myocardial infarction, cerebrovascular accidents, and systemic hypertension have all been linked to it. The pseudoexfoliative condition was first reported with the characteristic findings of white or grey flakes on the anterior lens capsule, the prevalence of glaucoma rising with age, and its presence in about 50% of eyes. A few decades later, the term pseudoexfoliation was given to differentiate it from the true exfoliation syndrome. True exfoliation syndrome is characterized by lamellar delamination of the lens capsule and is caused by exposure to infrared radiation. It is commonly seen in glassblowers. Age is a risk factor for PEX once a person reaches 70. Symptoms of PEX include elevated intraocular pressure, peripapillary transillumination deficiencies, potential glaucomatous optic nerve damage, poor dilatation, Sampaolesi line, and fibrillar white flaky deposits along the pupillary border. Meanwhile, fibrillar white flaky deposits on the anterior lens capsule (Hoarfrost Ring) and pigment dispersion syndrome are not pathognomonic.
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Affiliation(s)
- Rajal R Bora
- Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Roshan Prasad
- Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Swapneel Mathurkar
- Ophthalmology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Kashish Bhojwani
- Pathology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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Kapuganti RS, Alone DP. Current understanding of genetics and epigenetics in pseudoexfoliation syndrome and glaucoma. Mol Aspects Med 2023; 94:101214. [PMID: 37729850 DOI: 10.1016/j.mam.2023.101214] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 09/08/2023] [Accepted: 09/13/2023] [Indexed: 09/22/2023]
Abstract
Pseudoexfoliation is a complex, progressive, and systemic age-related disorder. The early stage of deposition of extracellular fibrillar material on ocular and extraocular tissues is termed as pseudoexfoliation syndrome (PEXS). The severe advanced stage is known as pseudoexfoliation glaucoma (PEXG), which involves increased intraocular pressure and optic nerve damage. Through genome-wide association and candidate gene studies, PEX has been associated with numerous genetic risk variants in various gene loci. However, the genetic basis of the disease fails to explain certain features of PEX pathology, such as the progressive nature of the disease, asymmetric ocular manifestation, age-related onset, and only a subset of PEXS individuals developing PEXG. Increasing evidence shows an interplay of genetic and epigenetic factors in the pathology of complex, multifactorial diseases. In this review, we have discussed the genetic basis of the disease and the emerging contribution of epigenetic regulations in PEX pathogenesis, focusing on DNA methylation and non-coding RNAs. Aberrant methylation patterns, histone modifications, and post-transcriptional regulation by microRNAs lead to aberrant gene expression changes. We have reviewed these aberrant epigenetic changes in PEX pathology and their effect on molecular pathways associated with PEX. We have further discussed some possible genetic/epigenetic-based diagnoses and therapeutics for PEX. Although studies to understand the role of epigenetic regulations in PEX are just emerging, epigenetic modifications contribute significantly to PEX pathogenesis and may pave the way for better and targeted therapeutics.
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Affiliation(s)
- Ramani Shyam Kapuganti
- School of Biological Sciences, National Institute of Science Education and Research (NISER) Bhubaneswar, P.O. Bhimpur-Padanpur, Jatni, Khurda, Odisha, 752050, India; Homi Bhabha National Institute (HBNI), Training School Complex, Anushaktinagar, Mumbai, 400094, India
| | - Debasmita Pankaj Alone
- School of Biological Sciences, National Institute of Science Education and Research (NISER) Bhubaneswar, P.O. Bhimpur-Padanpur, Jatni, Khurda, Odisha, 752050, India; Homi Bhabha National Institute (HBNI), Training School Complex, Anushaktinagar, Mumbai, 400094, India.
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Washington J, Ritch R, Liu Y. Homocysteine and Glaucoma. Int J Mol Sci 2023; 24:10790. [PMID: 37445966 DOI: 10.3390/ijms241310790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Revised: 06/10/2023] [Accepted: 06/11/2023] [Indexed: 07/15/2023] Open
Abstract
Elevated levels of homocysteine (Hcy), a non-proteinogenic amino acid, may lead to a host of manifestations across the biological systems, particularly the nervous system. Defects in Hcy metabolism have been associated with many neurodegenerative diseases including glaucoma, i.e., the leading cause of blindness. However, the pathophysiology of elevated Hcy and its eligibility as a risk factor for glaucoma remain unclear. We aimed to provide a comprehensive review of the relationship between elevated Hcy levels and glaucoma. Through a systemic search of the PubMed and Google Scholar databases, we found that elevated Hcy might play an important role in the pathogenesis of glaucoma. Further research will be necessary to help clarify the specific contribution of elevated Hcy in the pathogenesis of glaucoma. A discovery and conceptual understanding of Hcy-associated glaucoma could be the keys to providing better therapeutic treatment, if not prophylactic treatment, for this disease.
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Affiliation(s)
- Joshua Washington
- Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
| | - Robert Ritch
- New York Eye & Ear Infirmary, New York, NY 10003, USA
| | - Yutao Liu
- Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
- James & Jean Culver Vision Discovery Institute, 4 Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
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Koklesova L, Mazurakova A, Samec M, Biringer K, Samuel SM, Büsselberg D, Kubatka P, Golubnitschaja O. Homocysteine metabolism as the target for predictive medical approach, disease prevention, prognosis, and treatments tailored to the person. EPMA J 2021; 12:477-505. [PMID: 34786033 PMCID: PMC8581606 DOI: 10.1007/s13167-021-00263-0] [Citation(s) in RCA: 83] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 10/29/2021] [Indexed: 02/07/2023]
Abstract
Homocysteine (Hcy) metabolism is crucial for regulating methionine availability, protein homeostasis, and DNA-methylation presenting, therefore, key pathways in post-genomic and epigenetic regulation mechanisms. Consequently, impaired Hcy metabolism leading to elevated concentrations of Hcy in the blood plasma (hyperhomocysteinemia) is linked to the overproduction of free radicals, induced oxidative stress, mitochondrial impairments, systemic inflammation and increased risks of eye disorders, coronary artery diseases, atherosclerosis, myocardial infarction, ischemic stroke, thrombotic events, cancer development and progression, osteoporosis, neurodegenerative disorders, pregnancy complications, delayed healing processes, and poor COVID-19 outcomes, among others. This review focuses on the homocysteine metabolism impairments relevant for various pathological conditions. Innovative strategies in the framework of 3P medicine consider Hcy metabolic pathways as the specific target for in vitro diagnostics, predictive medical approaches, cost-effective preventive measures, and optimized treatments tailored to the individualized patient profiles in primary, secondary, and tertiary care.
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Affiliation(s)
- Lenka Koklesova
- Clinic of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia
| | - Alena Mazurakova
- Clinic of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia
| | - Marek Samec
- Jessenius Faculty of Medicine in Martin, Biomedical Centre Martin, Comenius University in Bratislava, Mala Hora 4D, 036 01 Martin, Slovakia
| | - Kamil Biringer
- Clinic of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia
| | - Samson Mathews Samuel
- Department of Physiology and Biophysics, Weill Cornell Medicine in Qatar, Education City, Qatar Foundation, 24144 Doha, Qatar
| | - Dietrich Büsselberg
- Department of Physiology and Biophysics, Weill Cornell Medicine in Qatar, Education City, Qatar Foundation, 24144 Doha, Qatar
| | - Peter Kubatka
- Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia
| | - Olga Golubnitschaja
- Predictive, Preventive, Personalised (3P) Medicine, Department of Radiation Oncology, University Hospital Bonn, Rheinische Friedrich-Wilhelms-Universität Bonn, 53127 Bonn, Germany
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Aziz BF, Elawamry AI, Roshdy MM, Tawfik CA. Exfoliation Syndrome in Egypt: Prevalence and Association with Cataract in a Large Cohort. Ophthalmol Ther 2021; 10:1045-1056. [PMID: 34580841 PMCID: PMC8589887 DOI: 10.1007/s40123-021-00397-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 09/07/2021] [Indexed: 11/26/2022] Open
Abstract
INTRODUCTION Exfoliation syndrome is an age-related disease leading to ocular and systemic complications. We aimed to evaluate the prevalence of exfoliation syndrome (XFS) in Egypt and its association with cataract as one of its comorbidities. METHODS In a retrospective, hospital-based study, 155,032 Egyptians aged over 40 years from all 27 Egyptian governorates were evaluated for the prevalence of XFS and cataract in the period between January 2015 and June 2020. RESULTS A total of 2448 (1.6%) of the studied subjects had XFS. Their mean age was 71.2 ± 9.62 years which was significantly higher than those of subjects with no XFS. Men comprised 1348 (55.1%) of those diagnosed with XFS and this association was statistically significant (OR 1.57, 95% CI 1.45-1.70). Considering the ratio between subjects in our cohort from each region and its real population, the overall corrected prevalence in Egypt was 4.49% (Territorial regions 6.89%, Upper Egypt 5.51%, Lower Egypt 4.38%, and Greater Cairo 3.29%). Among all subjects with XFS, cataract was found in 2150 subjects (87.8%) and XFS represented 6.4% of all subjects diagnosed with cataract in our cohort (n = 33,610). Among subjects with no cataract (n = 121,422), 298 subjects had XFS (OR 0.04, 95% CI 0.03-0.04). CONCLUSION Egypt has a moderate XFS prevalence compared to other countries. There is a strong association between XFS and cataract, and XFS was more common in elderly males. The results can be explained by differences in diet, ethnicity, climate, and maybe other factors.
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Affiliation(s)
- Bassem Fayez Aziz
- Faculty of Medicine, Ain Shams University, Cairo, Egypt.
- Watany Eye Hospital, Cairo, Egypt.
- Bassem Fayez Clinic, 50 Al Khalifa Al Mamoun St., Roxy, Heliopolis, Cairo, Egypt.
| | - Amr Ismail Elawamry
- Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Watany Eye Hospital, Cairo, Egypt
| | - Maged Maher Roshdy
- Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Watany Eye Hospital, Cairo, Egypt
| | - Caroline Atef Tawfik
- Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Watany Eye Hospital, Cairo, Egypt
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Cueto AFV, Álvarez L, García M, Álvarez-Barrios A, Artime E, Cueto LFV, Coca-Prados M, González-Iglesias H. Candidate Glaucoma Biomarkers: From Proteins to Metabolites, and the Pitfalls to Clinical Applications. BIOLOGY 2021; 10:763. [PMID: 34439995 PMCID: PMC8389649 DOI: 10.3390/biology10080763] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 08/05/2021] [Accepted: 08/08/2021] [Indexed: 12/17/2022]
Abstract
Glaucoma is an insidious group of eye diseases causing degeneration of the optic nerve, progressive loss of vision, and irreversible blindness. The number of people affected by glaucoma is estimated at 80 million in 2021, with 3.5% prevalence in people aged 40-80. The main biomarker and risk factor for the onset and progression of glaucoma is the elevation of intraocular pressure. However, when glaucoma is diagnosed, the level of retinal ganglion cell death usually amounts to 30-40%; hence, the urgent need for its early diagnosis. Molecular biomarkers of glaucoma, from proteins to metabolites, may be helpful as indicators of pathogenic processes observed during the disease's onset. The discovery of human glaucoma biomarkers is hampered by major limitations, including whether medications are influencing the expression of molecules in bodily fluids, or whether tests to validate glaucoma biomarker candidates should include human subjects with different types and stages of the disease, as well as patients with other ocular and neurodegenerative diseases. Moreover, the proper selection of the biofluid or tissue, as well as the analytical platform, should be mandatory. In this review, we have summarized current knowledge concerning proteomics- and metabolomics-based glaucoma biomarkers, with specificity to human eye tissue and fluid, as well the analytical approach and the main results obtained. The complex data published to date, which include at least 458 different molecules altered in human glaucoma, merit a new, integrative approach allowing for future diagnostic tests based on the absolute quantification of local and/or systemic biomarkers of glaucoma.
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Affiliation(s)
- Andrés Fernández-Vega Cueto
- Instituto Oftalmológico Fernández-Vega, Avda. Dres. Fernández-Vega, 34, 33012 Oviedo, Spain; (A.F.-V.C.); (M.G.)
- Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, Universidad de Oviedo, 33012 Oviedo, Spain; (L.Á.); (A.Á.-B.); (E.A.)
| | - Lydia Álvarez
- Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, Universidad de Oviedo, 33012 Oviedo, Spain; (L.Á.); (A.Á.-B.); (E.A.)
| | - Montserrat García
- Instituto Oftalmológico Fernández-Vega, Avda. Dres. Fernández-Vega, 34, 33012 Oviedo, Spain; (A.F.-V.C.); (M.G.)
- Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, Universidad de Oviedo, 33012 Oviedo, Spain; (L.Á.); (A.Á.-B.); (E.A.)
| | - Ana Álvarez-Barrios
- Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, Universidad de Oviedo, 33012 Oviedo, Spain; (L.Á.); (A.Á.-B.); (E.A.)
| | - Enol Artime
- Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, Universidad de Oviedo, 33012 Oviedo, Spain; (L.Á.); (A.Á.-B.); (E.A.)
| | - Luis Fernández-Vega Cueto
- Instituto Oftalmológico Fernández-Vega, Avda. Dres. Fernández-Vega, 34, 33012 Oviedo, Spain; (A.F.-V.C.); (M.G.)
- Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, Universidad de Oviedo, 33012 Oviedo, Spain; (L.Á.); (A.Á.-B.); (E.A.)
| | - Miguel Coca-Prados
- Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06510, USA;
| | - Héctor González-Iglesias
- Instituto Oftalmológico Fernández-Vega, Avda. Dres. Fernández-Vega, 34, 33012 Oviedo, Spain; (A.F.-V.C.); (M.G.)
- Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, Universidad de Oviedo, 33012 Oviedo, Spain; (L.Á.); (A.Á.-B.); (E.A.)
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Talebnejad MR, Azimi A, Khalili MR, Meshksar A. The Role of Trace Elements in Pseudoexfoliation Syndrome: A Cross-sectional Study. J Ophthalmic Vis Res 2021; 16:165-170. [PMID: 34055253 PMCID: PMC8126740 DOI: 10.18502/jovr.v16i2.9079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Accepted: 01/08/2020] [Indexed: 11/24/2022] Open
Abstract
Purpose Pseudoexfoliation syndrome (PXF) is an age-related condition, characterized by deposition of whitish flake-shaped materials in the anterior segment of the eye. Although it occurs all over the world, a considerable racial variation exists. According to the high frequency of PXF in Iran and the importance of prevention and early treatment, we evaluated the plasma level of iron, zinc, copper, and magnesium in patients with PXF. Methods In this study, 83 individuals were enrolled; 40 patients with cataract and PXF as the case group and 43 age- and sex-matched individuals with cataract but without PXF as the control group. The serum levels of the mentioned microelements were compared in two groups. Results In the case group, 25 (62.5%) male and 15 (37.5%) female subjects participated. In the control group, the corresponding figures were 22 (51.2%) and 21 (48.8%), respectively. The mean age of the case group was 66.07 ± 9.46 and that for the control group was 66.88 ± 8.04 years. Regarding the case group, the serum levels of iron, zinc, copper, and magnesium were 60.58 ± 21.04, 84.7 ± 14.37, 120.23 ± 14.43, and 2.11 ± 0.23, respectively. These serum levels in the control group were 89.07 ± 26.06, 97.51 ± 17.42, 123.33 ± 19.01, and 2.14 ± 0.16. The serum levels of iron and zinc were significantly lower in the case group than the control group (P< 0.0001); however, such a difference was not observed in terms of copper and magnesium serum levels. Conclusion Our study demonstrated that the serum iron and zinc levels were lower in PXF patients. Nutritional deficiency may be a cause of zonular weakness in these patients. Heme is a cofactor for the enzyme which contributes to the biosynthesis of fibrillin, the major protein in zonular fibers. Therefore, iron can play a substantial role in the biosynthesis of the fibrils and also in the zonular stability.
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Affiliation(s)
- Mohammad Reza Talebnejad
- Poostchi Ophthalmology Research Center, Department of Ophthalmology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Azimi
- Poostchi Ophthalmology Research Center, Department of Ophthalmology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Reza Khalili
- Poostchi Ophthalmology Research Center, Department of Ophthalmology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Aidin Meshksar
- Poostchi Ophthalmology Research Center, Department of Ophthalmology, Shiraz University of Medical Sciences, Shiraz, Iran
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Relationship between homocysteine levels, anterior chamber depth, and pseudoexfoliation glaucoma in patients with pseudoexfoliation. Int Ophthalmol 2020; 40:1731-1737. [PMID: 32212027 DOI: 10.1007/s10792-020-01341-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Accepted: 03/13/2020] [Indexed: 10/24/2022]
Abstract
PURPOSE This study investigates the relationship between plasma homocysteine levels, anterior chamber depth (ACD), and pseudoexfoliation glaucoma (PEXG) in patients with pseudoexfoliation syndrome. METHODS Sixty patients (F:M = 35:25) with pseudoexfoliation (PEX) were divided into two groups based on their plasma homocysteine levels; group 1 (< 20 µmol/L, normal) and group 2 (≥ 20 µmol/L, high). Intraocular pressure (IOP) and ACD values as well as plasma homocysteine levels were compared between the two groups. Moreover, the mean values for ACD and IOP were compared between patients stratified according to the reference upper limit for the homocysteine level (above and below 14 μmol/L), and the prevalence of high IOP was estimated. RESULTS Groups 1 and 2 showed no statistically significant differences in the mean ACD (3.04 ± 0.28 vs. 3.07 ± 0.31 mm, respectively) and mean IOP (20.63 ± 10.22 vs. 21.67 ± 7.55 mmHg, respectively). Patients with PEX and homocysteine levels > 14 μmol/L had a significantly increased prevalence (P < 0.05) of high IOP (≥ 22 mmHg). CONCLUSIONS Patients with PEX and high homocysteine levels have an increased prevalence of high IOP. No relationship exists between plasma homocysteine levels and ACD. Thus, PEXG should be suspected in patients with PEX and high plasma homocysteine levels. Plasma homocysteine levels could be helpful for the diagnosis of PEXG, although larger sample studies are required to confirm this finding.
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Abstract
In this review, we present an update on biomarkers (both clinical and laboratory) on the basis of recent peer-reviewed publications relating to pseudoexfoliation syndrome and pseudoexfoliation glaucoma.
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12
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Atalay K, Savur F, Kirgiz A, Kaldırım H, Zengi O. Serum levels of thyroid hormone, vitamin D, vitamin B12, folic acid, C-reactive protein, and hemoglobin in Pseudoexfoliation and primary open angle Glaucoma. J Fr Ophtalmol 2019; 42:730-738. [DOI: 10.1016/j.jfo.2019.01.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2018] [Revised: 01/16/2019] [Accepted: 01/17/2019] [Indexed: 12/25/2022]
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Hyperhomocysteinemia Causes Chorioretinal Angiogenesis with Placental Growth Factor Upregulation. Sci Rep 2018; 8:15755. [PMID: 30361676 PMCID: PMC6202361 DOI: 10.1038/s41598-018-34187-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Accepted: 10/12/2018] [Indexed: 02/03/2023] Open
Abstract
Hyperhomocysteinemia is a risk factor for atherosclerosis, which may also be associated with retinal vascular disease, diabetic retinopathy, retinal vein occlusion, and glaucoma. For this study, we established a hyperhomocysteinemia animal model to explore homocysteine (hcy)-related choroidal angiogenesis and possible related factors. We injected Sprague Dawley (SD) rats with different concentrations of hcy and performed color fundus imaging, fluorescein angiography, image-guided optical coherence tomography, and retinal histology to observe the retinal and choroidal changes. Subsequently, we observed prominent choroidal vasculature with congested and tortuous retinal and choroidal vessels in fundus angiographies of the hyperhomocysteinemia animal model. In the histological study, the choroidal capillaries proliferated in the hcy-treated eyes, mimicking choroidal neovascularization. Disrupted retinal pigment epithelium (RPE), abnormal branching vascular network (BVN), and polyp-like structures were also observed in the hcy-treated eyes. Furthermore, we found that placental growth factor (PlGF), but not vascular epithelial growth factor (VEGF), was the key mediating factor of this phenomenon. Our findings suggest that hyperhomocysteinemia might cause choroidal angiogenesis.
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Abstract
Caffeine, a popular psychostimulant that acts as an adenosine receptor antagonist, is the most widely used drug in history, consumed daily by people worldwide. Knowledge of the physiological and pathological effects of caffeine is crucial in improving public health because of its widespread use. We provide a summary of the current evidence on the effect of caffeine on the eye. Most of the research conducted to date is in relation to cataract and glaucoma, two of the most common eye diseases among the elderly.
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Rebecca M, Gayathri R, Bhuvanasundar R, Sripriya K, Shantha B, Angayarkanni N. Elastin modulation and modification by homocysteine: a key factor in the pathogenesis of Pseudoexfoliation syndrome? Br J Ophthalmol 2018; 103:985-992. [PMID: 30249767 DOI: 10.1136/bjophthalmol-2018-312088] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Revised: 08/03/2018] [Accepted: 08/07/2018] [Indexed: 01/25/2023]
Abstract
BACKGROUND Pseudoexfoliation syndrome (PXF) is an idiopathic, elastogenesis-associated systemic disease characterised by amyloid-like material aggregates in the eye. Elevated plasma and aqueous humour (aqH) homocysteine (Hcy) is reportedly associated with PXF. This study is aimed to probe Hcy-mediated alterations in elastin expression. METHODOLOGY Lens level of Hcy (total Hcy (tHcy)), mRNA expression of Eln, CBS and MTR in lens capsule, protein expression of elastin in aqH were estimated by enzyme immunoassay, quantitative PCR and western blot, respectively in PXF, PXF with glaucoma (PXF-G) cases, in comparison with cataract-alone disease controls. Human lens epithelial cells (hLECs) were exposed to Hcy and homocysteine thiolactone (HCTL) to evaluate elastin expression in vitro. Furthermore, elastin recombinant protein was incubated with Hcy and HCTL to assess secondary and tertiary structural modifications based on circular dichroism spectroscopy, spectrophotometric and SEM studies. RESULTS The lens tHcy was significantly high in PXF (p=0.02) and PXF-G (p=0.009). Eln expression was elevated in PXF and PXF-G (p=0.0007). Elastin level in aqH was elevated in PXF (p=0.01) and PXF-G (p=0.002). Hcy (200 µM) and HCTL (1 µM) promoted elastin expression at mRNA level by 36-fold (p=0.02) and 10-fold (p=0.05), respectively, and at protein level by nearly two-fold in cultured hLECs. Secondary structure changes in elastin protein caused by Hcy were evident from 34.11% drop in α-helix and 6.17% gain in β-sheet. Fluorescence, spectral assays and SEM analyses showed aggregation and amyloid formation of elastin with homocysteinylation. CONCLUSION The study reveals that lens accumulation of Hcy associated with hyperhomocysteinaemia is characteristic of PXF that augments elastin expression. Hcy causes structural changes promoting elastin aggregation, thereby contributing to defective elastin in PXF and PXF-G.
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Affiliation(s)
- Manohar Rebecca
- RS Mehta Jain Department of Biochemistry and Cell Biology, KBIRVO block, Vision Research Foundation, Sankara Nethralaya, Chennai, Tamil Nadu, India.,Tamil Nadu Dr MGR Medical University, Chennai, Tamil Nadu, India
| | - Ramakrishnan Gayathri
- RS Mehta Jain Department of Biochemistry and Cell Biology, KBIRVO block, Vision Research Foundation, Sankara Nethralaya, Chennai, Tamil Nadu, India
| | - Renganathan Bhuvanasundar
- RS Mehta Jain Department of Biochemistry and Cell Biology, KBIRVO block, Vision Research Foundation, Sankara Nethralaya, Chennai, Tamil Nadu, India
| | - Krishnamoorthy Sripriya
- Smt. Jadhavbai Nathamal Singhvee Glaucoma Services, Medical Research Foundation, Sankara Nethralaya, Chennai, Tamil Nadu, India
| | - Balekudaru Shantha
- Smt. Jadhavbai Nathamal Singhvee Glaucoma Services, Medical Research Foundation, Sankara Nethralaya, Chennai, Tamil Nadu, India
| | - Narayanasamy Angayarkanni
- RS Mehta Jain Department of Biochemistry and Cell Biology, KBIRVO block, Vision Research Foundation, Sankara Nethralaya, Chennai, Tamil Nadu, India
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Zhou Z, Liang Y, Qu H, Zhao M, Guo F, Zhao C, Teng W. Plasma homocysteine concentrations and risk of intracerebral hemorrhage: a systematic review and meta-analysis. Sci Rep 2018; 8:2568. [PMID: 29416106 PMCID: PMC5803270 DOI: 10.1038/s41598-018-21019-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 01/29/2018] [Indexed: 12/27/2022] Open
Abstract
Intracerebral hemorrhage (ICH) has the highest mortality rate in all strokes. However, controversy still exists concerning the association between plasma homocysteine (Hcy) and ICH. A systematic review and meta-analysis was conducted using Pubmed, Embase, and Web of Science up to April 18, 2017. Standard mean difference (SMD) for mean differences of plasma Hcy levels with 95% confidence intervals (CI) was calculated. Seven studies including 667 ICH patients and 1821 ischemic stroke patients were identified for meta-analysis. Our results showed that Hcy levels in ICH patients were significantly higher than those in healthy controls (SMD = 0.59, 95% CI = 0.51–0.68, P < 0.001); no statistic differences were found in the comparisons of Hcy levels between ICH and ischemic stroke (SMD = −0.03, 95% CI = −0.13–0.06, P > 0.05); further subgroup analysis of ethnicity (Asians: SMD = 0.57, 95% CI = 0.48–0.66, P < 0.001; Caucasians: SMD = 0.77, 95% CI = 0.51–1.02, P < 0.001) and sample size (small samples: SMD = 0.55, 95% CI = 0.30–0.80, P < 0.001; large samples size: SMD = 0.60, 95% CI = 0.51–0.69, P < 0.001) in relation to Hcy levels between ICH and healthy controls did not change these results. In conclusion, Hcy level may be an aggravating factor in atherosclerosis, which is positively associated with high risk of ICH. Race-specific differences between Asians and Caucasians have no impact on the risk of ICH.
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Affiliation(s)
- Zhike Zhou
- Department of Geriatrics, The First Affiliated Hospital, China Medical University, Shenyang, 110001, Liaoning, PR China
| | - Yifan Liang
- Department of Neurology, The First Affiliated Hospital, China Medical University, Shenyang, 110001, Liaoning, PR China
| | - Huiling Qu
- 3Department of Neurology, The People's Hospital of Liaoning Province, Shenyang, 110016, Liaoning, PR China
| | - Mei Zhao
- Department of Cardiology, The Shengjing Affiliated Hospital, China Medical University, Shenyang, 110004, Liaoning, PR China
| | - Feng Guo
- Department of Neurology, Fuxin Central Hospital, fuxin, 123000, Liaoning, PR China
| | - Chuansheng Zhao
- Department of Neurology, The First Affiliated Hospital, China Medical University, Shenyang, 110001, Liaoning, PR China.
| | - Weiyu Teng
- Department of Neurology, The First Affiliated Hospital, China Medical University, Shenyang, 110001, Liaoning, PR China.
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Li S, Li D, Shao M, Cao W, Sun X. Lack of Association between Serum Vitamin B₆, Vitamin B 12, and Vitamin D Levels with Different Types of Glaucoma: A Systematic Review and Meta-Analysis. Nutrients 2017. [PMID: 28635642 PMCID: PMC5490615 DOI: 10.3390/nu9060636] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Although vitamins play a major role in health, and their deficiency may be linked to symptoms of optic-nerve dysfunction, the association between serum vitamin levels and glaucoma in humans remains controversial. In this study, articles in the PubMed, Web of Science, and EMBASE databases were searched up to 25March 2017. Nine studies on primary open-angle glaucoma (POAG), four studies on normal tension glaucoma (NTG), and six studies on exfoliative glaucoma (EXG) were retrieved. The combined results showed no differences in the levels of serum vitamin B6 between POAG (p = 0.406) and EXG (p = 0.139) patients and controls. The weighted mean differences (WMDs) with 95% confidence intervals (CIs) were 2.792 ng/mL (−3.793 to 9.377) and 1.342 ng/mL (−3.120 to 0.436), respectively. There was no difference between POAG (p = 0.952), NTG (p = 0.757), or EXG (p = 0.064) patients and controls in terms of serum vitamin B12. The WMDs with 95% CIs were 0.933 pg/mL (−31.116 to 29.249), 6.652 pg/mL (−35.473 to 48.777), and 49.946 pg/mL (−102.892 to 3.001), respectively. The serum vitamin D levels exhibited no differences (p = 0.064) between POAG patients and controls; the WMD with 95% CI was 2.488 ng/mL (−5.120 to 0.145). In conclusion, there was no association found between serum vitamin B6, vitamin B12, or vitamin D levels and the different types of glaucoma.
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Affiliation(s)
- Shengjie Li
- Department of Clinical Laboratory, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China.
| | - Danhui Li
- Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Medical School, Xi'an Jiaotong University, Xi'an 710061, China.
| | - Mingxi Shao
- Department of Clinical Laboratory, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China.
| | - Wenjun Cao
- Department of Clinical Laboratory, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China.
- Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China.
| | - Xinghuai Sun
- Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China.
- State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200031, China.
- Key Laboratory of Myopia, Ministry of Health, Fudan University, Shanghai 200031, China.
- Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai 200031, China.
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Turgut Coban D, Cakir T, Erol MK, Dogan G, Dogan B, Bilgilisoy Filiz M, Toraman NF. Electroneuromyographic findings in pseudoexfoliation syndrome. Int Ophthalmol 2017; 38:705-712. [PMID: 28405788 DOI: 10.1007/s10792-017-0520-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Accepted: 04/04/2017] [Indexed: 12/13/2022]
Abstract
PURPOSE To examine peripheral electroneuromyographic findings in patients with ocular pseudoexfoliation syndrome (PEX) and to compare them controls without PEX. METHODS A case-control study design was used to examine 31 patients with PEX and compare the findings with those of 31 age- and sex-matched healthy controls. All patients underwent complete ophthalmologic examination that included peripheral electroneuromyography examination. Motor and sensorial nerve conduction of the median, ulnar, tibial, peroneal, and sural nerve and the sympathetic skin response were measured. RESULTS The average sensorial nerve latency of the ulnar and sural nerve was significantly longer in the PEX group compared to the control group (p < 0.05). The average sensorial nerve conduction amplitude and the velocity of the ulnar and sural nerve were significantly lower in the PEX group (p < 0.05). DISCUSSION Peripheral nerves, especially sensorial fibers, appear to be affected in PEX patients. These finding may indicate that PEX is a systemic disease.
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Affiliation(s)
- Deniz Turgut Coban
- Department of Ophthalmology, Antalya Education and Research Hospital, Antalya, Turkey.
| | - Tuncay Cakir
- Department of Physical Medicine and Rehabilitation, Antalya Education and Research Hospital, Antalya, Turkey
| | - Muhammet Kazim Erol
- Department of Ophthalmology, Antalya Education and Research Hospital, Antalya, Turkey
| | - Gulsum Dogan
- Department of Physical Medicine and Rehabilitation, Antalya Education and Research Hospital, Antalya, Turkey
| | - Berna Dogan
- Department of Ophthalmology, Antalya Education and Research Hospital, Antalya, Turkey
| | - Meral Bilgilisoy Filiz
- Department of Physical Medicine and Rehabilitation, Antalya Education and Research Hospital, Antalya, Turkey
| | - Naciye Fusun Toraman
- Department of Physical Medicine and Rehabilitation, Antalya Education and Research Hospital, Antalya, Turkey
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Aboobakar IF, Johnson WM, Stamer WD, Hauser MA, Allingham RR. Major review: Exfoliation syndrome; advances in disease genetics, molecular biology, and epidemiology. Exp Eye Res 2016; 154:88-103. [PMID: 27845061 DOI: 10.1016/j.exer.2016.11.011] [Citation(s) in RCA: 98] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2016] [Revised: 10/06/2016] [Accepted: 11/10/2016] [Indexed: 12/20/2022]
Abstract
Exfoliation syndrome (XFS) is a common age-related disorder that leads to deposition of extracellular fibrillar material throughout the body. The most recognized disease manifestation is exfoliation glaucoma (XFG), which is a common cause of blindness worldwide. Recent developments in XFS genetics, cell biology and epidemiology have greatly improved our understanding of the etiology of this complex inherited disease. This review summarizes current knowledge of XFS pathogenesis, identifies gaps in knowledge, and discusses areas for future research.
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Affiliation(s)
- Inas F Aboobakar
- Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA
| | - William M Johnson
- Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA
| | - W Daniel Stamer
- Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA
| | - Michael A Hauser
- Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA
| | - R Rand Allingham
- Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA.
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Association of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with primary glaucoma in Saudi population. BMC Ophthalmol 2016; 16:156. [PMID: 27585654 PMCID: PMC5009653 DOI: 10.1186/s12886-016-0337-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2015] [Accepted: 08/23/2016] [Indexed: 11/18/2022] Open
Abstract
Background Methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate metabolism is involved in DNA synthesis, DNA repair and DNA methylation. The functional polymorphism of MTHFR gene, C677T has been shown to impact various diseases and implicated as a risk factor for the development of various neurodegenerative disorders including glaucoma. Methods We investigated MTHFR C677T genotypes and alleles frequencies in primary glaucoma [primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG)] patients and matched healthy controls in a case-control study. Two hundred ten primary glaucoma cases were studied for MTHFR C677T polymorphism and compared with 280 controls taken from the healthy population, employing the polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP). The MTHFR gene was amplified using specific primers. The PCR products (294 bp) was subsequently digested with HinfI (New England Biolabs) at 37 °C for 12 h, separated by electrophoresis on 2 % agarose gels, and visualized with ethidium bromide staining. The restriction digestion yielded 168 and 126 bp fragments for TT, 294, 168 and 126 bp fragments for CT and undigested PCR product 294 bp indicating CC genotype. Results We found the frequency of the genotypes and alleles of MTHFR C677T differ significantly between cases and controls. The frequencies of allele T and genotype CT were significantly higher while the frequencies of allele C and genotype CC were lower in primary glaucoma patients as compared to controls (p <0.05). Upon stratification of our results into POAG and PACG, significantly higher frequencies of allele T (19.44 %) and genotype CT (38.89 %) were found in POAG patients compared to controls (12.5 % and 25 % respectively). The frequencies of alleles and genotypes were almost similar in PACG and controls (p = 0.8). Conclusion This study indicates that the allele T and genotype CT of MTHFR C677T polymorphism are significantly associated with POAG while allele C and CC genotype may be protective for it. We conclude that the MTHFR C677T polymorphism increases the risk for POAG development in Saudi population and can be a genetic marker however, further studies are needed with multiple-ethnic populations affected with POAG to strengthen these findings.
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21
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Gu BY, Chu JH, Lim SH, Cha SC. Analysis of Serum Homocysteine and Risk of Coronary Heart Disease in Patients with Pseudoexfoliation Syndrome. JOURNAL OF THE KOREAN OPHTHALMOLOGICAL SOCIETY 2016. [DOI: 10.3341/jkos.2016.57.3.461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Affiliation(s)
- Byoung Young Gu
- Department of Ophthalmology, Yeungnam University College of Medicine, Daegu, Korea
| | - Ji Hee Chu
- Department of Ophthalmology, Yeungnam University College of Medicine, Daegu, Korea
| | - Su Ho Lim
- Department of Ophthalmology, Daegu Veterans Hospital, Daegu, Korea
| | - Soon Cheol Cha
- Department of Ophthalmology, Yeungnam University College of Medicine, Daegu, Korea
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22
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Abdolrahimzadeh S, Fameli V, Mollo R, Contestabile MT, Perdicchi A, Recupero SM. Rare Diseases Leading to Childhood Glaucoma: Epidemiology, Pathophysiogenesis, and Management. BIOMED RESEARCH INTERNATIONAL 2015; 2015:781294. [PMID: 26451378 PMCID: PMC4588342 DOI: 10.1155/2015/781294] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/26/2015] [Accepted: 04/22/2015] [Indexed: 11/17/2022]
Abstract
Noteworthy heterogeneity exists in the rare diseases associated with childhood glaucoma. Primary congenital glaucoma is mostly sporadic; however, 10% to 40% of cases are familial. CYP1B1 gene mutations seem to account for 87% of familial cases and 27% of sporadic cases. Childhood glaucoma is classified in primary and secondary congenital glaucoma, further divided as glaucoma arising in dysgenesis associated with neural crest anomalies, phakomatoses, metabolic disorders, mitotic diseases, congenital disorders, and acquired conditions. Neural crest alterations lead to the wide spectrum of iridocorneal trabeculodysgenesis. Systemic diseases associated with childhood glaucoma include the heterogenous group of phakomatoses where glaucoma is frequently encountered in the Sturge-Weber syndrome and its variants, in phakomatosis pigmentovascularis associated with oculodermal melanocytosis, and more rarely in neurofibromatosis type 1. Childhood glaucoma is also described in systemic disorders of mitotic and metabolic activity. Acquired secondary glaucoma has been associated with uveitis, trauma, drugs, and neoplastic diseases. A database research revealed reports of childhood glaucoma in rare diseases, which do not include glaucoma in their manifestation. These are otopalatodigital syndrome, complete androgen insensitivity, pseudotrisomy 13, Brachmann-de Lange syndrome, acrofrontofacionasal dysostosis, caudal regression syndrome, and Wolf-Hirschhorn syndrome.
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Affiliation(s)
- Solmaz Abdolrahimzadeh
- Ophthalmology Unit, DAI Head/Neck, Umberto I Policlinic, University of Rome “Sapienza”, Viale del Policlinico 155, 00161 Rome, Italy
| | - Valeria Fameli
- Ophthalmology Unit, Department of Sense Organs, University of Rome “Sapienza”, Viale del Policlinico 155, 00161 Rome, Italy
| | - Roberto Mollo
- Ophthalmology Unit, DAI Head/Neck, Umberto I Policlinic, University of Rome “Sapienza”, Viale del Policlinico 155, 00161 Rome, Italy
| | - Maria Teresa Contestabile
- Ophthalmology Unit, St. Andrea Hospital, NESMOS Department, University of Rome “Sapienza”, via di Grottarossa 1035-1039, 00189 Rome, Italy
| | - Andrea Perdicchi
- Ophthalmology Unit, St. Andrea Hospital, NESMOS Department, University of Rome “Sapienza”, via di Grottarossa 1035-1039, 00189 Rome, Italy
| | - Santi Maria Recupero
- Ophthalmology Unit, St. Andrea Hospital, NESMOS Department, University of Rome “Sapienza”, via di Grottarossa 1035-1039, 00189 Rome, Italy
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Fu HJ, Zhao LB, Xue JJ, Wu ZX, Huang YP, Liu W, Gao Z. Elevated Serum Homocysteine (Hcy) Levels May Contribute to the Pathogenesis of Cerebral Infarction. J Mol Neurosci 2015; 56:553-61. [DOI: 10.1007/s12031-015-0497-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2014] [Accepted: 01/14/2015] [Indexed: 11/24/2022]
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Zacharaki F, Hadjigeorgiou GM, Koliakos GG, Morrison MA, Tsezou A, Chatzoulis DZ, Almpanidou P, Topouridou K, Karabatsas CH, Pefkianaki M, DeAngelis MM, Tsironi EE. Plasma homocysteine and genetic variants of homocysteine metabolism enzymes in patients from central Greece with primary open-angle glaucoma and pseudoexfoliation glaucoma. Clin Ophthalmol 2014; 8:1819-25. [PMID: 25246760 PMCID: PMC4166342 DOI: 10.2147/opth.s64904] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND The purpose of this study was to investigate plasma homocysteine levels and polymorphisms in genes encoding enzymes in the metabolic pathway of homocysteine in association with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXFG). METHODS A total of 156 glaucoma patients (76 with POAG and 80 with PXFG) and 135 controls matched for age and sex were enrolled in this study. Plasma homocysteine levels were measured using a commercially available enzyme-linked immunosorbent assay kit. DNA was extracted from peripheral blood leukocytes and real-time polymerase chain reaction was performed for genotyping of the samples. Patients were genotyped using predesigned TaqMan(®) single nucleotide polymorphism genotyping assays for two exon variations (rs1801131, rs1801133) in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and one intron variation (rs8006686) in the methylenetetrahydrofolate dehydrogenase (MTHFD1) gene. RESULTS Homocysteine levels were slightly higher in the patient group (POAG and PXFG) compared with controls, but the difference did not reach statistical significance. The minor alleles of the MTHFR single nucleotide polymorphisms showed a protective effect for POAG and showed an increased risk for PXFG, but none of these associations reached statistical significance (P>0.05). The minor allele of MTHFD1 rs8006686 showed a trend for increased risk of both POAG and PXFG (P>0.05). No statistically significant interaction was seen between the genetic variants and homocysteine levels (P>0.05). CONCLUSION Our results show that neither the examined single nucleotide polymorphisms from genes involved in the pathway of homocysteine metabolism nor the measured homocysteine levels were associated with POAG or PXFG in our study cohort.
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Affiliation(s)
- Fani Zacharaki
- Department of Ophthalmology, Faculty of Medicine, University of Thessaly, Larissa, Greece
| | | | - Georgios G Koliakos
- Department of Biochemistry, Medical School, Aristotles University of Thessaloniki, Thessaloniki, Greece
| | - Margaux A Morrison
- Department of Ophthalmology and Visual Sciences, John A Moran Eye Center, University of Utah, Salt Lake City, UT, USA
| | - Aspasia Tsezou
- Department of Biology, Faculty of Medicine, University of Thessaly, Larissa, Greece
| | - Dimitrios Z Chatzoulis
- Department of Ophthalmology, Faculty of Medicine, University of Thessaly, Larissa, Greece
| | - Pavlina Almpanidou
- Department of Ophthalmology, Faculty of Medicine, University of Thessaly, Larissa, Greece
| | - Konstantina Topouridou
- Department of Biochemistry, Medical School, Aristotles University of Thessaloniki, Thessaloniki, Greece
| | | | - Maria Pefkianaki
- Department of Ophthalmology, Faculty of Medicine, University of Thessaly, Larissa, Greece
| | - Margaret M DeAngelis
- Department of Ophthalmology and Visual Sciences, John A Moran Eye Center, University of Utah, Salt Lake City, UT, USA
| | - Evangelia E Tsironi
- Department of Ophthalmology, Faculty of Medicine, University of Thessaly, Larissa, Greece
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Andrikopoulos GK, Alexopoulos DK, Gartaganis SP. Pseudoexfoliation syndrome and cardiovascular diseases. World J Cardiol 2014; 6:847-854. [PMID: 25228963 PMCID: PMC4163713 DOI: 10.4330/wjc.v6.i8.847] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2013] [Revised: 04/09/2014] [Accepted: 06/11/2014] [Indexed: 02/06/2023] Open
Abstract
Pseudoexfoliation (PEX) syndrome is a well-recognized late-onset disease caused by a generalized fibrillopathy. It is linked to a broad spectrum of ocular complications including glaucoma and perioperative problems during cataract surgery. Apart from the long-known intraocular manifestations, PEX deposits have been found in a variety of extraocular locations and they appear to represent a systemic process associated with increased cardiovascular and cerebrovascular morbidity. However, as published results are inconsistent, the clinical significance of the extraocular PEX deposits remains controversial. Identification of PEX deposits in the heart and the vessel wall, epidemiologic studies, as well as, similarities in pathogenetic mechanisms have led to the hypothesis of a possible relation between fibrillar material and cardiovascular disease. Recent studies suggest that PEX syndrome is frequently linked to impaired heart and blood vessels function. Systemic and ocular blood flow changes, altered parasympathetic vascular control and baroreflex sensitivity, increased vascular resistance and decreased blood flow velocity, arterial endothelial dysfunction, high levels of plasma homocysteine and arterial hypertension have all been demonstrated in PEX subjects. Common features in the pathogenesis of both atherosclerosis and PEX, like oxidative stress and inflammation and a possible higher frequency of abdominal aorta aneurysm in PEX patients, could imply that these grey-white deposits and cardiovascular disorders are related or reflect different manifestations of the same process.
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Kang JH, Loomis SJ, Wiggs JL, Willett WC, Pasquale LR. A prospective study of folate, vitamin B₆, and vitamin B₁₂ intake in relation to exfoliation glaucoma or suspected exfoliation glaucoma. JAMA Ophthalmol 2014; 132:549-59. [PMID: 24699833 DOI: 10.1001/jamaophthalmol.2014.100] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
IMPORTANCE Effective strategies for primary prevention are lacking for exfoliation glaucoma (EG), which is the most common type of secondary glaucoma. OBJECTIVE To examine the association between B vitamin intake and EG or suspected EG (EG/SEG) risk. DESIGN, SETTING, AND PARTICIPANTS National prospective cohort study using more than 20 years of follow-up data from the Nurses' Health Study (all female registered nurses) and the Health Professionals Follow-up Study (all male health professionals) from June 1, 1980, to May 31, 2010 (Nurses' Health Study) and January 1, 1986, to December 31, 2010 (Health Professionals Follow-up Study). We included a subset of 78,980 Nurses' Health Study women and 41,221 Health Professionals Follow-up Study men who were 40 years or older, free of glaucoma, had completed diet questionnaires, and reported eye examinations (follow-up rate, >85%). EXPOSURES Cumulatively updated intake of B vitamins (folate, vitamin B6, and vitamin B12) as ascertained by repeated administration of validated questionnaires. MAIN OUTCOMES AND MEASURES Incident cases of EG/SEG, totaling 399 (329 women and 70 men), were first identified with the questionnaires and were subsequently confirmed with medical records. Multivariable relative risks for EG/SEG were calculated in each cohort and then pooled with meta-analysis. RESULTS Vitamin B₆ and vitamin B₁₂ intake was not associated with EG/SEG risk in pooled analyses (P = .52 and P = .99 for linear trend, respectively). However, a suggestive trend of a reduced risk was observed with higher intake of folate: compared with the lowest quintile of cumulatively averaged updated total folate intake, the multivariable relative risk for EG/SEG for the highest quintile (≥654 μg/d) was 0.75 (95% CI, 0.54-1.04; P = .02 for linear trend). These results were not materially altered after adjustment for vitamin B₆ and vitamin B₁₂ intake. An association was observed for supplemental folate intake but not for dietary folate only (P = .03 and P = .64 for linear trend, respectively). Greater frequency of multivitamin use showed a modest suggestive inverse association (current multivitamin use of ≥6 times per week vs nonuse multivariable relative risk, 0.84; 95% CI, 0.64-1.11; P = .06 for linear trend). CONCLUSIONS AND RELEVANCE Higher total folate intake was associated with a suggestive lower risk for EG/SEG, supporting a possible causal role of homocysteine in EG/SEG.
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Affiliation(s)
- Jae H Kang
- Channing Division of Network Medicine, Department of Medicine, Brigham & Women's Hospital, and Harvard Medical School, Boston, Massachusetts
| | | | - Janey L Wiggs
- Glaucoma Service, Massachusetts Eye and Ear, Boston, Massachusetts
| | - Walter C Willett
- Channing Division of Network Medicine, Department of Medicine, Brigham & Women's Hospital, and Harvard Medical School, Boston, Massachusetts3Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts4Department of Epidemiology, Harvar
| | - Louis R Pasquale
- Channing Division of Network Medicine, Department of Medicine, Brigham & Women's Hospital, and Harvard Medical School, Boston, Massachusetts2Glaucoma Service, Massachusetts Eye and Ear, Boston, Massachusetts
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The frequency of exfoliation syndrome in the central anatolia region of Turkey. J Ophthalmol 2014; 2014:139826. [PMID: 25165574 PMCID: PMC4140104 DOI: 10.1155/2014/139826] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2014] [Accepted: 06/05/2014] [Indexed: 02/08/2023] Open
Abstract
Aim. The aim of this study was to investigate the frequency of exfoliation syndrome in the Central Anatolia region of Turkey and to evaluate its relationship with cardiovascular and ocular diseases. Methods. Patients over the age of 45 years who presented to the clinic were included in the study. All cases underwent a comprehensive ophthalmology examination. Exfoliation syndrome was diagnosed with the presence of exfoliative material on the lens anterior capsule or iris on slit lamp examination. The patients were divided into two groups as the exfoliation syndrome group and nonexfoliation syndrome group according to the presence of exfoliative material. Results. Exfoliative material was found in one or both eyes of 212 of the 2103 patients (10.1%) evaluated within the scope of the study. A significant relationship was found between exfoliation syndrome and increasing age and male gender. A significant relationship was found between exfoliation syndrome and glaucoma, cataracts, age-related macular degeneration, and phacodonesis. While no relationship was found between exfoliation syndrome and hypertension or diabetes mellitus, a significant relationship was found with coronary artery disease. Conclusion.
The unilateral or bilateral exfoliation syndrome frequency was 10.1% in this hospital-based study. A statistically significant relationship was found between exfoliation syndrome and advancing age, gender, and coronary artery disease.
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Bettis DI, Allingham RR, Wirostko BM. Systemic diseases associated with exfoliation syndrome. Int Ophthalmol Clin 2014; 54:15-28. [PMID: 25171641 DOI: 10.1097/iio.0000000000000044] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
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Medical Management of Exfoliative Glaucoma. Clin Ophthalmol 2014; 54:57-70. [DOI: 10.1097/iio.0000000000000043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Katsi V, Pavlidis AN, Kallistratos MS, Fitsios A, Bratsas A, Tousoulis D, Stefanadis C, Manolis AJ, Kallikazaros I. Cardiovascular repercussions of the pseudoexfoliation syndrome. NORTH AMERICAN JOURNAL OF MEDICAL SCIENCES 2013; 5:454-459. [PMID: 24083219 PMCID: PMC3784921 DOI: 10.4103/1947-2714.117294] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Pseudoexfoliation syndrome is a primarily ophthalmological disorder caused by deposition of whitish-gray protein on the lens, iris, and multiple other eye tissues. There is increasing evidence over the previous years that pseudoexfoliation syndrome is a systemic disorder with various extraocular manifestations and has recently been linked to several cardiovascular disorders. The present article aims to summarize the current knowledge on cardiovascular implications of this well-described clinical entity.
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Affiliation(s)
- Vasiliki Katsi
- Department of Cardiology, Hippokration Hospital, Athens, Greece
| | | | | | | | - Athanasios Bratsas
- First Cardiology Department, Athens University Medical School, Athens, Greece
| | - Dimitris Tousoulis
- First Cardiology Department, Athens University Medical School, Athens, Greece
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Türkyılmaz K, Öner V, Kırbas A, Sevim MS, Sekeryapan B, Özgür G, Durmus M. Serum YKL-40 levels as a novel marker of inflammation and endothelial dysfunction in patients with pseudoexfoliation syndrome. Eye (Lond) 2013; 27:854-9. [PMID: 23661157 DOI: 10.1038/eye.2013.92] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2012] [Accepted: 04/10/2013] [Indexed: 02/08/2023] Open
Abstract
PURPOSE To evaluate serum levels of YKL-40 in patients with pseudoexfoliation syndrome (PEX) in comparison with those of age- and sex-matched healthy subjects. METHODS Forty patients with PEX (PEX group) and 40 age- and sex-matched control subjects (control group) were enrolled in the study. An enzyme immunoassay method using the commercially available test MicroVue YKL-40 was used to measure serum YKL-40 concentration. Systolic and diastolic blood pressures, serum levels of high sensitivity C-reactive protein (hsCRP), total cholesterol, low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglycerides were also examined. RESULTS The mean age was 54.4±7.6 (ranging 41-65) years in each group. The mean serum YKL-40 level of the PEX group was significantly higher than that of the control group (P<0.001). In addition, the mean serum HsCRP, total cholesterol, LDL, and triglycerides levels were significantly higher, and mean serum HDL level was significantly lower in the PEX group than in the control group (all P<0.001, excluding both P=0.002 for triglycerides and HDL levels). Further, the mean systolic and diastolic blood pressures were significantly higher in the PEX group than in the control group (P₁=0.001 and P₂=0.01, respectively). CONCLUSION We have shown a relationship between PEX and elevated serum levels of YKL-40. We imply that a better understanding of the role of YKL-40 in the pathogenesis of endothelial dysfunction and atherosclerosis is necessary to develop new therapies for preventing or treating PEX. Further studies are warranted to clarify the clinical relevance of these findings.
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Affiliation(s)
- K Türkyılmaz
- Department of Ophthalmology, Recep Tayyip Erdoğan University Medical School, Rize, Turkey.
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Xu F, Zhao X, Zeng SM, Li L, Zhong HB, Li M. Homocysteine, B Vitamins, Methylenetetrahydrofolate Reductase Gene, and Risk of Primary Open-Angle Glaucoma. Ophthalmology 2012; 119:2493-9. [DOI: 10.1016/j.ophtha.2012.06.025] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2012] [Revised: 06/15/2012] [Accepted: 06/15/2012] [Indexed: 11/25/2022] Open
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Pasquale LR, Wiggs JL, Willett WC, Kang JH. The Relationship between caffeine and coffee consumption and exfoliation glaucoma or glaucoma suspect: a prospective study in two cohorts. Invest Ophthalmol Vis Sci 2012; 53:6427-33. [PMID: 22918628 DOI: 10.1167/iovs.12-10085] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
PURPOSE We examined the association between caffeine and caffeinated beverage consumption in relation to the risk of exfoliation glaucoma or exfoliation glaucoma suspect (EG/EGS). METHODS We followed 78,977 women from the Nurses' Health Study (NHS) and 41,202 men from the Health Professionals Follow-up Study (HPFS) who were at least 40 years of age, did not have glaucoma, and reported undergoing eye examinations from 1980 (NHS) or 1986 (HPFS) to 2008. Information on consumption of caffeine-containing beverages and potential confounders were repeatedly ascertained in validated follow-up questionnaires. Confirmation with medical record review revealed 360 incident EG/EGS cases. Multivariate rate ratios (RRs) for EG/EGS were calculated in each cohort and then pooled using meta-analytic techniques. RESULTS Compared with participants whose cumulatively updated total caffeine consumption was <125 mg/day, participants who consumed ≥ 500 mg/day had a trend toward increased risk of EG/EGS that was not statistically significant (RR = 1.43; 95% confidence interval [CI], 0.98-2.08); P trend = 0.06). Compared to abstainers, those who drank ≥ 3 cups of caffeinated coffee daily were at increased risk of EG/EGS (RR = 1.66; 95% CI, 1.09-2.54; P trend = 0.02). These results were not materially altered after adjustment for total fluid intake. Associations were stronger among women with a family history of glaucoma (P interaction = 0.06 for coffee; P interaction = 0.03 for caffeine). We did not find associations with consumption of other caffeinated products (caffeinated soda, caffeinated tea, decaffeinated coffee or chocolate) and risk of EG/EGS (P trend ≥ 0.31). CONCLUSIONS We observed a positive association between heavier coffee consumption with risk of EG/EGS in this large prospective study.
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Affiliation(s)
- Louis R Pasquale
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA
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Djordjevic-Jocic J, Jovanovic P, Bozic M, Tasic A, Rancic Z. Prevalence and early detection of abdominal aortic aneurysm in pseudoexfoliation syndrome and pseudoexfoliation glaucoma. Curr Eye Res 2012; 37:617-23. [PMID: 22574663 DOI: 10.3109/02713683.2012.665120] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
PURPOSE The goals of this study were to demonstrate the frequency of infrarenal abdominal aortic aneurysm (AAA) in patients with pseudoexfoliation (PEX) syndrome (PEXS) and PEX glaucoma (PEXG), and to determine whether limited screening for AAA in specific subgroups of patients with PEX is reasonable and justifiable. MATERIALS AND METHODS This prospective study comprised 60 patients with PEXS and 60 with PEXG (examined group), and 60 patients with primary open-angle glaucoma (POAG) and 60 with cataract (control group). Clinical ophthalmic examination included slit-lamp biomicroscopy of the anterior segment and direct slit-lamp gonioscopy (using a Goldmann three-mirror lens) of the anterior chamber angle. All patients underwent routine Color Doppler duplex ultrasonography of the infrarenal aorta and iliac arteries. RESULTS There was a statistically significant difference (p < 0.05) between the PEXG group and control group vis-a-vis presence of AAA, which occurred more frequently in patients with greater amounts of angle pigmentation (p < 0.05). Univariate logistic regression analysis indicated statistically significant associations between AAA and PEX (p < 0.01), angle pigmentation (p < 0.05), gender (p < 0.01), diabetes mellitus (DM) (p < 0.05), and arterial hypertension (AHT) (p < 0.01). Multivariate regression analysis, adjusted to gender and age, showed that the most important clinical parameters related to AAA in patients with PEXS and PEXG are gender, presence of PEX, DM, and AHT (p < 0.05). CONCLUSION The frequency of AAA is significantly higher in patients with PEXS and PEXG than in patients with POAG or cataract. Restricted screening for AAA in male PEXS patients, who also have elevated degrees of angle pigmentation, arterial hypertension, and DM, is clinically warranted.
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Affiliation(s)
- Jasmina Djordjevic-Jocic
- Medical Faculty University of Nis, Ophthalmology Clinic, Clinical Center Nis, Serbia. jdjordjevic.jocic@ gmail.com
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Age-related changes in visual function in cystathionine-beta-synthase mutant mice, a model of hyperhomocysteinemia. Exp Eye Res 2011; 96:124-31. [PMID: 22197750 DOI: 10.1016/j.exer.2011.12.011] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2011] [Revised: 12/06/2011] [Accepted: 12/09/2011] [Indexed: 11/24/2022]
Abstract
Homocysteine is an amino acid required for the metabolism of methionine. Excess homocysteine is implicated in cardiovascular and neurological disease and new data suggest a role in various retinopathies. Mice lacking cystathionine-beta-synthase (cbs(-/-)) have an excess of retinal homocysteine and develop anatomical abnormalities in multiple retinal layers, including photoreceptors and ganglion cells; heterozygous (cbs(+/-)) mice demonstrate ganglion cell loss and mitochondrial abnormalities in the optic nerve. The purpose of the present study was to determine whether elevated homocysteine, due to absent or diminished cbs, alters visual function. We examined cbs(-/-) (3 weeks) and cbs(+/-) mice (5, 10, 15, 30 weeks) and results were compared to those obtained from wild type (WT) littermates. Conventional dark- and light-adapted ERGs were recorded, along with dc-ERG to assess retinal pigment epithelial (RPE) function. The visual evoked potential (VEP) was used to assess transmission to the visual cortex. The amplitudes of the major ERG components were reduced in cbs(-/-) mice at age 3 weeks and VEPs were delayed markedly. These findings are consistent with the early retinal disruption observed anatomically in these mice. In comparison, at 3 weeks of age, responses of cbs(+/-) mice did not differ significantly from those of WT mice. Functional abnormalities were not observed in cbs(+/-) mice until 15 weeks of age, at which time amplitude reductions were noted for the ERG a- and b-wave and the light peak component, but not for other components generated by the RPE. VEP implicit times were delayed in cbs(+/-) mice at 15 and 30 weeks, while VEP amplitudes were unaffected. The later onset of functional defects in cbs(+/-) mice is consistent with a slow loss of ganglion cells reported previously in the heterozygous mutant. Light peak abnormalities indicate that RPE function is also compromised in older cbs(+/-) mice. The data suggest that severe elevations of homocysteine are associated with marked alterations of retinal function while modest homocysteine elevation is reflected in milder and delayed alterations of retinal function. The work lays the foundation to explore the role of homocysteine in retinal diseases such as glaucoma and optic neuropathy.
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Xu F, Zhang L, Li M. Plasma homocysteine, serum folic acid, serum vitamin B12, serum vitamin B6, MTHFR and risk of pseudoexfoliation glaucoma: a meta-analysis. Graefes Arch Clin Exp Ophthalmol 2011; 250:1067-74. [DOI: 10.1007/s00417-011-1877-4] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2011] [Revised: 11/06/2011] [Accepted: 11/15/2011] [Indexed: 12/29/2022] Open
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