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Kheirollahi A, Sadeghi S, Orandi S, Moayedi K, Khajeh K, Khoobi M, Golestani A. Chondroitinase as a therapeutic enzyme: Prospects and challenges. Enzyme Microb Technol 2024; 172:110348. [PMID: 37898093 DOI: 10.1016/j.enzmictec.2023.110348] [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: 05/22/2023] [Revised: 09/28/2023] [Accepted: 10/19/2023] [Indexed: 10/30/2023]
Abstract
The chondroitinases (Chase) are bacterial lyases that specifically digest chondroitin sulfate and/or dermatan sulfate glycosaminoglycans via a β-elimination reaction and generate unsaturated disaccharides. In recent decades, these enzymes have attracted the attention of many researchers due to their potential applications in various aspects of medicine from the treatment of spinal cord injury to use as an analytical tool. In spite of this diverse spectrum, the application of Chase is faced with several limitations and challenges such as thermal instability and lack of a suitable delivery system. In the current review, we address potential therapeutic applications of Chase with emphasis on the challenges ahead. Then, we summarize the latest achievements to overcome the problems by considering the studies carried out in the field of enzyme engineering, drug delivery, and combination-based therapy.
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Affiliation(s)
- Asma Kheirollahi
- Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Solmaz Sadeghi
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Shirin Orandi
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Kiana Moayedi
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Khosro Khajeh
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran 14115-154, Iran
| | - Mehdi Khoobi
- Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Abolfazl Golestani
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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Ho CPS, Lai TYY. Pharmacotherapy for Choroidal Neovascularization Due to Uncommon Causes. Curr Pharm Des 2019; 24:4882-4895. [PMID: 30727875 DOI: 10.2174/1381612825666190206105943] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Accepted: 01/18/2019] [Indexed: 11/22/2022]
Abstract
BACKGROUND Choroidal neovascularization (CNV) in adults is most commonly associated with neovascular age-related macular degeneration (AMD) and pathologic myopia. Though less common, CNV can also develop from other conditions such as uveitis, central serous chorioretinopathy, angioid streaks, intraocular tumors, hereditary chorioretinal dystrophies, or can be idiopathic in origin. If left untreated, CNV may cause visual loss because of exudation of intraretinal or subretinal fluid, retinal or subretinal hemorrhage, or fibrosis involving the macula. It is well known that one of the main drivers of angiogenesis in CNV development is vascular endothelial growth factor (VEGF) and therefore inhibitors of VEGF might be an effective treatment for CNV. METHODS The goal of this review is to provide an overview and summary in the use of pharmacotherapy especially anti-VEGF therapy, in the treatment of CNV due to uncommon causes. RESULTS Results from uncontrolled case series and controlled clinical trials have reported good efficacy and safety in using anti-VEGF agents including bevacizumab, ranibizumab, aflibercept and ziv-aflibercept in the treatment of CNV due to uncommon causes. Anti-VEGF has also been used in combination with verteporfin PDT and anti-inflammatory agents for treating CNV of various causes. CONCLUSION Pharmacotherapy with anti-VEGF agents is an effective treatment option for CNV due to uncommon etiologies.
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Affiliation(s)
- Christine P S Ho
- Faculty of Medicine, The University of Hong Kong, Kowloon, Hong Kong
| | - Timothy Y Y Lai
- Hong Kong Eye Hospital, Department of Ophthalmology & Visual Sciences, The Chinese University of Hong Kong, Kowloon, Hong Kong.,2010 Retina & Macula Centre, Kowloon, Hong Kong
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Prospero Ponce CM, Stevenson W, Gelman R, Agarwal DR, Christoforidis JB. Ocriplasmin: who is the best candidate? Clin Ophthalmol 2016; 10:485-95. [PMID: 27051270 PMCID: PMC4803238 DOI: 10.2147/opth.s97947] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
Abstract
Enzymatic vitreolysis is currently the focus of attention around the world for treating vitreomacular traction and full-thickness macular hole. Induction of posterior vitreous detachment is an active area of developmental clinical and basic research. Despite exerting an incompletely elucidated physiological effect, ocriplasmin (also known as microplasmin) has been recognized to serve as a well-tolerated intravitreal injection for the treatment of vitreomacular traction and full-thickness macular hole. There are several unexplored areas of intervention where enzymatic vitreolysis could potentially be used (ie, diabetic macular edema). Recent promising studies have included combinations of enzymatic approaches and new synthetic molecules that induce complete posterior vitreous detachment as well as antiangiogenesis. Although no guidelines have been proposed for the use of ocriplasmin, this review attempts to aid physicians in answering the most important question, "Who is the best candidate?"
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Affiliation(s)
- Claudia M Prospero Ponce
- Retina Division, Department of Ophthalmology, University of Arizona Medical Center, Tucson, AZ, USA
| | - William Stevenson
- Retina Division, Department of Ophthalmology, University of Arizona Medical Center, Tucson, AZ, USA
| | - Rachel Gelman
- Retina Division, Department of Ophthalmology, University of Arizona Medical Center, Tucson, AZ, USA
| | - Daniel R Agarwal
- Retina Division, Department of Ophthalmology, University of Arizona Medical Center, Tucson, AZ, USA
| | - John B Christoforidis
- Retina Division, Department of Ophthalmology, University of Arizona Medical Center, Tucson, AZ, USA
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Chuang CC, Chen SN. Induction of Posterior Vitreous Detachment in Pediatric Vitrectomy by Preoperative Intravitreal Injection of Tissue Plasminogen Activator. J Pediatr Ophthalmol Strabismus 2016; 53:113-8. [PMID: 27018884 DOI: 10.3928/01913913-20160209-01] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Accepted: 01/01/2016] [Indexed: 11/20/2022]
Abstract
PURPOSE To report the efficacy of intravitreal injection of tissue plasminogen activator (tPA) with or without autoserum in induction of posterior vitreous detachment (PVD) in pediatric vitrectomy. METHODS Retrospective, interventional case series of pediatric patients receiving intravitreal injection of tPA preoperatively to facilitate PVD in vitrectomy from January 2011 to December 2014 at the Changhua Christian Hospital, Taiwan. All patients received intravitreal injections of 25 µg of tPA 3 days before vitrectomy. For cases without preexisting vitreous hemorrhage, 0.1 mL of intravitreal autologous serum was co-administered. Main outcome measures included successful rate of posterior vitreous detachment in vitrectomy, visual outcome, and related ocular complications. RESULTS Four boys and 2 girls were included. Ages ranged from 39 weeks' postmenstrual age to 8 years. The indications for vitrectomy were traumatic macular hole (cases 1 and 2); premacular hemorrhage secondary to retinopathy of prematurity (case 3); abusive head trauma with premacular hemorrhage, subinternal limiting membrane hemorrhage, and macular hole (case 4); trauma with dense vitreous hemorrhage (case 5); and vitreous hemorrhage with unknown cause (case 6). Successful PVD was induced intraoperatively in all cases and the macular hole was closed successfully in 3 of 3 cases (cases 1, 2, and 4). No surgical complications were noted. Visual outcome improved in all 3 eyes with checkable preoperative visual acuity (cases 1, 2, and 6). CONCLUSIONS Intravitreal injection of tPA 3 days before vitrectomy may be a helpful adjunct to induce pediatric PVD.
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Koleva-Georgieva DN. Pharmacologic vitreolysis: New strategy for treatment of anomalous vitreo-macular adhesion. World J Ophthalmol 2015; 5:99-105. [DOI: 10.5318/wjo.v5.i3.99] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2015] [Revised: 04/30/2015] [Accepted: 07/17/2015] [Indexed: 02/06/2023] Open
Abstract
Persistent anomalous vitreo-macular adhesion (VMA) is a well-known factor, associated with a variety of sight threatening diseases - including macular hole, vitreo-macular traction syndrome, cystoid and diabetic macular edema, exudative age- related macular degeneration, myopic traction maculopathy and others. With the advent of optical coherence tomography our understanding of these pathologies and the ability of their early diagnosis has gone much far in the past two decades. The release of macular traction has been of exclusive surgical capability. Notwithstanding good results, vitrectomy is hampered by the inability of complete vitreo-retinal separation (i.e., smooth, bare internal limiting membrane), compulsory postoperative positioning in macular hole cases, surgical complications, and high costs. With aim to offer less invasive and safe treatment modality for anomalous VMA, investigators have made enormous progress in the past decade. Leading among the studied nonsurgical measures is the intravitreal application of pharmacologic agents for the induction of vitreo-retinal separation and vitreous liquefaction, a method termed pharmacologic vitreolysis. Several vitreolytic agents have been studied to date, the most potent among them proved to be plasmin. Recently, ocriplasmin (formerly known as microplasmin) - a more stable than plasmin recombinant product, proved to be safe and efficient in releasing VMA in large studies, and consequently received FDA approval. It’s role in clinical practice is now in the process of being determined. This paper aims to review and summarize the current knowledge and status of investigation on this new approach for the treatment of VMA.
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Girach A, Pakola S. Vitreomacular interface diseases: pathophysiology, diagnosis and future treatment options. EXPERT REVIEW OF OPHTHALMOLOGY 2014. [DOI: 10.1586/eop.12.34] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Bandello F, La Spina C, Iuliano L, Fogliato G, Parodi MB. Review and perspectives on pharmacological vitreolysis. ACTA ACUST UNITED AC 2013; 230:179-85. [PMID: 24029751 DOI: 10.1159/000354547] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2013] [Accepted: 06/19/2013] [Indexed: 11/19/2022]
Abstract
The vitreous is involved in multiple diseases when an incomplete posterior vitreous detachment (PVD) occurs. An incomplete PVD can lead to several pathological conditions. Such visually threatening conditions are traditionally of exclusive surgical interest. In contrast, pharmacological vitreolysis is the effort to reduce or eliminate the pathogenetic role of the vitreous solely by means of drug delivery. Here we aim to review and summarize the evidence available to date about this challenging new approach.
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Affiliation(s)
- Francesco Bandello
- Department of Ophthalmology, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy
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Abstract
PURPOSE To discuss the potential role of microplasmin (ocriplasmin) as a surgical adjunct to vitrectomy in pediatric vitreoretinopathies. METHODS Literature review of the laboratory and clinical evidence to date for the use of both autologous plasmin enzyme as an adjunct to vitrectomy and more recently recombinant microplasmin (ocriplasmin) as monotherapy for focal vitreomacular traction in adults. RESULTS Autologous plasmin enzyme is currently being used as a surgical adjunct to vitrectomy, with supporting Levels 2 and 3 published evidence in a range of pediatric vitreoretinopathies including Stage 5 retinopathy of prematurity and congenital X-linked retinoschisis. The availability of autologous plasmin enzyme is limited. In recent Phase 3 clinical trials, intravitreal ocriplasmin versus sham injection resulted in resolution of focal vitreomacular traction in 27% versus 10% (P < 0.001, n = 652). CONCLUSION Ocriplasmin may potentially be used as a surgical adjunct to vitrectomy in place of autologous plasmin enzyme. A Phase 2, randomized, placebo-controlled surgical trial is under way to assess this.
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Schneider EW, Johnson MW. Emerging nonsurgical methods for the treatment of vitreomacular adhesion: a review. Clin Ophthalmol 2011; 5:1151-65. [PMID: 21887098 PMCID: PMC3162296 DOI: 10.2147/opth.s14840] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2011] [Indexed: 12/18/2022] Open
Abstract
With the dissemination of optical coherence tomography over the past two decades, the role of persistent vitreomacular adhesion (VMA) in the development of numerous macular pathologies - including idiopathic macular hole, vitreomacular traction syndrome, cystoid and diabetic macular edema, neovascularization in diabetic retinopathy and retinal vein occlusion, exudative age-related macular degeneration, and myopic traction maculopathy - has been established. While invasive vitreoretinal procedures have long been utilized to address complications related to these disorders, such an approach is hampered by incomplete vitreoretinal separation and vitreous removal, surgical complications, and high costs. In light of such limitations, investigators have increasingly looked to nonsurgical means for the treatment of persistent pathologic VMA. Chief among these alternative measures is the intravitreal application of pharmacologic agents for the induction of vitreous liquefaction and/or vitreoretinal separation, an approach termed pharmacologic vitreolysis. This article aims to review the available evidence regarding the use of pharmacologic agents in the treatment of VMA-related pathology. In addition, a discussion of vitreous molecular organization and principles of physiologic posterior vitreous detachment is provided to allow for a consideration of vitreolytic agent mode of action and molecular targets.
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Affiliation(s)
- Eric W Schneider
- Department of Ophthalmology and Visual Sciences, University of Michigan, WK Kellogg Eye Center, Ann Arbor, MI, USA
| | - Mark W Johnson
- Department of Ophthalmology and Visual Sciences, University of Michigan, WK Kellogg Eye Center, Ann Arbor, MI, USA
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Hermel M, Dailey W, Hartzer MK. Efficacy of plasmin, microplasmin, and streptokinase-plasmin complex for the in vitro degradation of fibronectin and laminin- implications for vitreoretinal surgery. Curr Eye Res 2010; 35:419-24. [PMID: 20450255 DOI: 10.3109/02713680903572517] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
PURPOSE Plasmin enzyme generates vitreoretinal separation by degradation of laminin and fibronectin in the vitreoretinal interface. It can be activated from plasminogen by urokinase, tissue plasminogen activator, or by formation of a 1:1 complex with streptokinase. The latter is then converted into a streptokinase-plasmin-complex (SK-P), which displays fibrinolytic activity and can generate free plasmin by proteolysis of plasminogen. We compared the efficacy of SK-P, SK-P activated plasmin, urokinase activated plasmin (UK-P), and microplasmin, a truncated form of plasmin, in cleaving laminin and fibronectin. METHODS Streptokinase (SK) was added to human plasminogen in molar ratios between 1:100 and 2:1, generating SK-P at ratios > 1:1, and mixtures of SK-P and free plasmin (SK-P/plasmin) at lower ratios. SK-PL, SK-P/plasmin, UK-P, and microplasmin were added to laminin and fibronectin, incubated at 37 degrees C for 30 min-22 hr and processed for SDS-PAGE. RESULTS Proteolysis using SK-activated plasminogen increased when the SK/plasminogen ratio was decreased, generating increasing amounts of free plasmin. Microplasmin and urokinase-activated plasmin displayed similar proteolysis of both laminin and fibronectin as SK/plasminogen at ratios of 1:10 or lower. CONCLUSION The mode of plasminogen activation influences the efficacy of proteolysis for laminin and fibronectin and should be considered when plasmin is used in vitreoretinal surgery.
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Affiliation(s)
- M Hermel
- Department of Ophthalmology, University of Aachen, Aachen, Germany.
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Hermel M, Dailey W, Trese M, Hartzer MK. A disposable system for rapid purification of autologous plasmin as an adjunct to vitrectomy — performance and safety profile. Graefes Arch Clin Exp Ophthalmol 2010; 249:37-46. [DOI: 10.1007/s00417-010-1466-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2010] [Revised: 06/21/2010] [Accepted: 07/12/2010] [Indexed: 11/28/2022] Open
Affiliation(s)
- Martin Hermel
- Department of Ophthalmology, RWTH Aachen University, Aachen, Germany.
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Abstract
PURPOSE OF REVIEW The field of vitreoretinal disease and surgery has seen tremendous growth and innovation in recent years. In view of the latest advances, the present article highlights some of the current trends in vitreoretinal research that promise to be revolutionary in the coming decade. RECENT FINDINGS Pharmacologic vitreolysis may greatly impact the current approach to treatment of various vitreoretinopathies. New methods of drug delivery to the posterior segment either via nanoparticles or sustained-release intravitreal implants may supplant repetitive intravitreal injections. Gene therapy may become more common as the genetic basis of inherited retinal diseases is further elucidated. Stem-cell transplantation and the implantation of artificial retinal prostheses offer promise for long-term sight restoration. SUMMARY Based on recent advances in ongoing vitreoretinal research, the spectrum of treatable retinal disease is likely to expand significantly in the coming decade, with enormous public health impact, as well as significant changes in the practice patterns of retina specialists worldwide.
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Hermel M, Prenner J, Alabdulrazzak M, Dailey W, Hartzer M. Effect of intravitreal plasmin on vitreous removal through a 25-gauge cutting system in the rabbit in vivo. Graefes Arch Clin Exp Ophthalmol 2008; 247:331-4. [PMID: 19034484 DOI: 10.1007/s00417-008-1000-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2008] [Revised: 10/18/2008] [Accepted: 10/29/2008] [Indexed: 02/01/2023] Open
Abstract
PURPOSE Intravitreal plasmin creates a posterior vitreous detachment, but may also liquefy the vitreous. This study measures the rate of vitreous removal from rabbit eyes after plasmin injection in vivo. METHODS Intravitreal injections of 150 IU hyaluronidase (n = 5), 0.5 activity units (AU, n = 6) or 0.9 AU of streptokinase-activated human plasmin (n = four groups of 6) in 0.1 ml were performed in rabbits, the fellow eyes received 0.1 ml BSS. After 30 min (hyaluronidase), 30 min, 4 h, 12 h or 24 h (0.9 AU plasmin) or 24 h (0.5 AU plasmin), 1 ml of vitreous was removed from each eye without infusion, using a 25-gauge cutter and a standardized protocol. Animals were sacrificed after surgery. RESULTS Compared to fellow eyes, the average rate of vitreous removal was increased by hyaluronidase by 68.9 +/- 6.3% (p < 0.05) and by 0.5 AU plasmin (24 h) by 26.8 +/- 3.3% (p < 0.05). 0.9 AU of plasmin increased removal rates by 0.8 +/- 10% (n.s.), 15.4 +/- 6.3% (p < 0.05), 40.3 +/- 3.1% (p < 0.05), and 71.9 +/- 32.4% (p < 0.05) after 30 min, 4 h, 12 h and 24 h incubation respectively. The ratios of removal rates of treated/control eyes in the 0.9 AU groups showed a linear correlation with incubation time (r = 0.783, p < 0.0001). CONCLUSION Intravitreal plasmin increases the rate of vitreous removal in rabbits.
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Affiliation(s)
- Martin Hermel
- Department of Ophthalmology, RWTH Aachen University, Pauwelsstrasse 30, 52057, Aachen, Germany.
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Preservation of structure and immunoreactivity at the vitreoretinal interface of the rabbit eye. Graefes Arch Clin Exp Ophthalmol 2008; 247:193-205. [DOI: 10.1007/s00417-008-0991-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2008] [Revised: 06/27/2008] [Accepted: 10/15/2008] [Indexed: 11/26/2022] Open
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Lim JW, Choi JH, Park IW. Intravitreal Tissue Plasminogen Activator with C3F8 Injection in Branch Retinal Vein Occlusion. JOURNAL OF THE KOREAN OPHTHALMOLOGICAL SOCIETY 2008. [DOI: 10.3341/jkos.2008.49.3.450] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Affiliation(s)
- Ji Won Lim
- Department of Ophthalmology, Hallym University Sacred Heart Hospital, Gyeonggi, Korea
| | - Jung Hoon Choi
- Department of Ophthalmology, Hallym University Sacred Heart Hospital, Gyeonggi, Korea
| | - In Won Park
- Department of Ophthalmology, Hallym University Sacred Heart Hospital, Gyeonggi, Korea
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Quiram PA, Leverenz VR, Baker RM, Dang L, Giblin FJ, Trese MT. Microplasmin-induced posterior vitreous detachment affects vitreous oxygen levels. Retina 2007; 27:1090-6. [PMID: 18040251 PMCID: PMC2702988 DOI: 10.1097/iae.0b013e3180654229] [Citation(s) in RCA: 79] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
PURPOSE To determine if enzymatic induction of a posterior vitreous detachment (PVD) and/or vitreous liquefaction affects O2 concentration in the vitreous cavity in animals with vascularized and avascular retinal circulations. METHODS Either microplasmin or hyaluronidase was injected intravitreally into guinea pigs (avascular retinal circulation), brown Norway rats (vascularized retinal circulation without fovea), or cats (vascularized retinal circulation with fovea) with the contralateral eye used as a control. One to 2 weeks post injection, vitreal oxygen concentration was measured using a highly sensitive, platinum-based fluorophore O2 sensor. In addition, control and microplasmin-injected rats, guinea pigs, and cats were exposed to 100% oxygen and vitreal O2 levels were measured over time. Scanning electron microscopy (SEM) was used to evaluate the vitreoretinal interface for the presence of a PVD. RESULTS In animals with a vascularized retinal circulation (brown Norway rats and cats), intravitreal injection of microplasmin with induction of a PVD significantly increased baseline O2 concentration in the vitreous cavity compared to hyaluronidase injected eyes and controls in rats (35, 25, and 23 mm Hg, P < 0.001 and P < 0.001, respectively) and cats (26, 18, and 16 mm Hg, P < 0.01 and P < 0.001, respectively). Interestingly, intravitreal injection of hyaluronidase (vitreous liquefaction without induction of a PVD) did not significantly increase vitreal O2 levels in any of the animal species (P > 0.1). Upon exposure to 100% oxygen by facemask, microplasmin injected animals showed a rapid increase in vitreal oxygen levels compared to hyaluronidase injected animals and controls, indicating that the presence of a PVD allows rapid O2 exchange within the vitreous cavity. Similarly, once O2 was discontinued, the O2 concentration decreased in a similarly rapid rate. SEM showed smooth retinal surfaces in microplasmin-injected cat eyes, indicating the presence of a PVD which was not present in hyaluronidase injected or control eyes. CONCLUSION The results suggest that enzymatic-assisted PVD with microplasmin increases vitreal O2 levels and increases the rate of O2 exchange within the vitreous cavity.
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Affiliation(s)
- Polly A Quiram
- Associated Retinal Consultants, Beaumont Hospital, Royal Oak, Michigan 48073, USA.
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