Age-related macular degeneration (AMD) is one of the most prevalent eye diseases among the ageing population worldwide. It is a leading cause of blindness in individuals over 55, particularly in industrialised Western countries. The prevalence of AMD increases with age, and genetic factors and environmental influences are believed to contribute to its development. Among the environmental factors, diet plays a significant role in AMD. This review explores the association between dietary components, dietary patterns and AMD. Various nutrients, non-nutrient substances and dietary models that have the potential to counteract oxidative stress and inflammation, which are underlying mechanisms of AMD, are discussed. Consuming fruits, vegetables, fish and seafood, whole grains, olive oil, nuts and low-glycaemic-index foods has been highlighted as beneficial for reducing the risk of AMD. Adhering to the Mediterranean diet, which encompasses these elements, can be recommended as a dietary pattern for AMD. Furthermore, the modulation of the gut microbiota through dietary interventions and probiotics has shown promise in managing AMD.

The gut microbiota represents a rich and adaptive microbial network inhabiting the gastrointestinal tract, performing key functions in nutrient processing, immune response modulation, intestinal wall protection, and microbial defense. Its composition remains highly personalized and responsive to external influences, including lifestyle patterns, physical activity, body composition, and nutritional intake. The interactions of the gut microbiota with bodily systems are conventionally interpreted as broad systemic impacts on organ balance. Yet, emerging research-exemplified by the gut microbiota-brain axis-suggests the potential existence of more targeted and direct communication mechanisms. Dysbiosis, characterized by microbial ecosystem disturbance, generates multiple metabolic compounds capable of entering systemic circulation and reaching distant tissues, notably including ocular structures. This microbial imbalance has been associated with both systemic and localized conditions linked to eye disorders. Accumulating scientific evidence now supports the concept of a gut-retina axis, underscoring the significant role of microbiota disruption in generating various retinal pathologies. This review comprehensively investigates gut microbiota composition, functional dynamics, and dysbiosis-induced alterations, with specific focus on retinal interactions in age-related macular degeneration, diabetic retinopathy, glaucoma, and retinal artery occlusion. Moreover, the review explores microbiota-targeted therapeutic strategies, including precision nutritional interventions and microbial transplantation, as potential modulators of retinal disease progression.

This scoping review aims to summarize the current state of knowledge on the potential involvement of infections in age-related macular degeneration (AMD).

Age-related macular degeneration is a multifactorial disease and the leading cause of vision loss among older adults in developed countries. Clarifying whether certain infections participate in its onset or progression seems essential, given the potential implications for treatment and prevention.

Using the PubMed database, we searched for articles in English, published until June 1, 2023, whose title and/or abstract contained terms related to AMD and infections. All types of study design, infectious agents, AMD diagnostic methods, and AMD stages were considered. Articles dealing with the oral and gut microbiota were not included but we provide a brief summary of high-quality literature reviews recently published on the subject.

Two investigators independently screened the 868 articles obtained by our algorithm and the reference lists of selected studies. In total, 40 articles were included, among which 30 on human data, 9 animal studies, 6 in vitro experiments, and 1 hypothesis paper (sometimes with several data types in the same article). Of these, 27 studies were published after 2010, highlighting a growing interest in recent years. A wide range of infectious agents has been investigated, including various microbiota (nasal, pharyngeal), 8 bacteria, 6 viral species, and 1 yeast. Among them, most have been investigated anecdotally. Only Chlamydia pneumoniae, Cytomegalovirus, and hepatitis B virus received more attention with 17, 6, and 4 studies, respectively. Numerous potential pathophysiological mechanisms have been discussed, including (1) an indirect role of infectious agents (i.e. a role of infections located distant from the eye, mainly through their interactions with the immune system) and (2) a direct role of some infectious agents implying potential infection of various cells types within AMD-related tissues.

Overall, this review highlights the diversity of possible interactions between infectious agents and AMD and suggests avenues of research to enrich the data currently available, which provide an insufficient level of evidence to conclude whether or not infectious agents are involved in this pathology.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

To explore the role of gut microbiota in preterm infants at high risk of developing retinopathy of prematurity (ROP).

Preterm infants with gestational age (GA) < 32 weeks and/or birth weight (BW) < 1500 g born between 2020 and 2021 were prospectively enrolled. Their faecal samples were collected and analysed at different postnatal ages of life using 16S rRNA gene sequencing on the Miseq platform. The main outcome measures were the microbial diversity, taxonomy, relative abundance, bacterial predicted functional analysis, and their associations with different ROP groups. Subgroup analyses were performed by matching their GA and BW across different ROP groups.

A total of 268 stool samples were collected from 110 preterm infants, including 13 with type 1 ROP, 44 with type 2 or mild ROP, and 53 without ROP. Type 1 ROP showed no significant difference in microbial diversity up to 8 postnatal weeks (p = 0.057), while type 2 and no ROP groups displayed increased diversity (p = 0.0015 and p = 0.049, respectively). Bifidobacterium genera was notably less abundant in type 1 ROP group at first postnatal week (p = 0.022) and remained low in subsequent weeks. Predicted functional analysis revealed enriched pathways in membrane transport, carbohydrate metabolism, amino acid metabolism, and replication and repair.

Reduced gut microbial diversity may be associated with ROP development in high-risk preterm infants. Further research is needed to comprehend how early-life Bifidobacterium reduction affects metabolism and how targeting microbiome may help for ROP prevention and management.

People are living longer and rates of age-related diseases such as age-related macular degeneration (AMD) are accelerating, placing enormous burdens on patients and health care systems. The quality of carbohydrate foods consumed by an individual impacts health. The glycemic index (GI) is a kinetic measure of the rate at which glucose arrives in the blood stream after consuming various carbohydrates. Consuming diets that favor slowly digested carbohydrates releases sugar into the bloodstream gradually after consuming a meal (low glycemic index). This is associated with reduced risk for major age-related diseases including AMD, cardiovascular disease, and diabetes. In comparison, consuming the same amounts of different carbohydrates in higher GI diets, releases glucose into the blood rapidly, causing glycative stress as well as accumulation of advanced glycation end products (AGEs). Such AGEs are cytotoxic by virtue of their forming abnormal proteins and protein aggregates, as well as inhibiting proteolytic and other protective pathways that might otherwise selectively recognize and remove toxic species. Using in vitro and animal models of glycative stress, we observed that consuming higher GI diets perturbs metabolism and the microbiome, resulting in a shift to more lipid-rich metabolomic profiles. Interactions between aging, diet, eye phenotypes and physiology were observed. A large body of laboratory animal and human clinical epidemiologic data indicates that consuming lower GI diets, or lower glycemia diets, is protective against features of early AMD (AMDf) in mice and AMD prevalence or AMD progression in humans. Drugs may be optimized to diminish the ravages of higher glycemic diets. Human trials are indicated to determine if AMD progression can be retarded using lower GI diets. Here we summarized the current knowledge regarding the pathological role of glycative stress in retinal dysfunction and how dietary strategies might diminish retinal disease.

The intricate interplay between the gut microbiota and ocular health has surpassed conventional medical beliefs, fundamentally reshaping our understanding of organ interconnectivity. This review investigates into the intricate relationship between gut microbiota-derived metabolites and their consequential impact on ocular health and disease pathogenesis. By examining the role of specific metabolites, such as short-chain fatty acids (SCFAs) like butyrate and bile acids (BAs), herein we elucidate their significant contributions to ocular pathologies, thought-provoking the traditional belief of organ sterility, particularly in the field of ophthalmology. Highlighting the dynamic nature of the gut microbiota and its profound influence on ocular health, this review underlines the necessity of comprehending the complex workings of the gut-eye axis, an emerging field of science ready for further exploration and scrutiny. While acknowledging the therapeutic promise in manipulating the gut microbiome and its metabolites, the available literature advocates for a targeted, precise approach. Instead of broad interventions, it emphasizes the potential of exploiting specific microbiome-related metabolites as a focused strategy. This targeted approach compared to a precision tool rather than a broad-spectrum solution, aims to explore the therapeutic applications of microbiome-related metabolites in the context of various retinal diseases. By proposing a nuanced strategy targeted at specific microbial metabolites, this review suggests that addressing specific deficiencies or imbalances through microbiome-related metabolites might yield expedited and pronounced outcomes in systemic health, extending to the eye. This focused strategy holds the potential in bypassing the irregularity associated with manipulating microbes themselves, paving a more efficient pathway toward desired outcomes in optimizing gut health and its implications for retinal diseases.

Omega-3 (n-3) polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), are required for the structure and function of the retina. Several observational studies indicate that consumption of a diet with relatively high levels of n-3 PUFAs, such as those provided by fish oils, has a protective effect against the development of age-related macular degeneration. Given the accumulating evidence showing the role of gut microbiota in regulating retinal physiology and host lipid metabolism, we evaluated the potential of long-term dietary supplementation with the Gram-positive bacterium Lactobacillus helveticus strain VEL12193 to modulate the retinal n-3 PUFA content. A set of complementary approaches was used to study the impact of such a supplementation on the gut microbiota and host lipid/fatty acid (FA) metabolism. L. helveticus-supplementation was associated with a decrease in retinal saturated FAs (SFAs) and monounsaturated FAs (MUFAs) as well as an increase in retinal n-3 and omega-6 (n-6) PUFAs. Interestingly, supplementation with L. helveticus enriched the retina in C22:5n-3 (docosapentaenoic acid, DPA), C22:6n-3 (DHA), C18:2n-6 (linoleic acid, LA) and C20:3n-6 (dihomo gamma-linolenic acid, DGLA). Long-term consumption of L. helveticus also modulated gut microbiota composition and some changes in OTUs abundance correlated with the retinal FA content. This study provides a proof of concept that targeting the gut microbiota could be an effective strategy to modulate the retinal FA content, including that of protective n-3 PUFAs, thus opening paths for the design of novel preventive and/or therapeutical strategies for retinopathies.

This study aims to investigate the effect of a systemic lipopolysaccharide (LPS) stimulus in the course of laser-induced choroidal neovascularization (CNV) in C57BL/6 J mice. A group of CNV-subjected mice received 1 mg/kg LPS via the tail vein immediately after CNV induction. Mouse eyes were monitored in vivo with fluorescein angiography for 2 weeks. In situ hybridization and flow cytometry were performed in the retina at different time points. LPS led to increased fluorescein leakage 3 days after CNV, correlated with a large influx of monocyte-derived macrophages and increase of pro-inflammatory microglia/macrophages in the retina. Additionally, LPS enhanced Vegfα mRNA expression by Glul-expressing cells but not Aif1 positive microglia/macrophages in the laser lesion. These findings suggest that systemic LPS exposure has transient detrimental effects in the course of CNV through activation of microglia/macrophages to a pro-inflammatory phenotype and supports the important role of these cells in the CNV course.

To examine disease progression in age-related macular degeneration (AMD) at 2 distinct stages, progression to geographic atrophy (GA) versus GA expansion, by comparison of the risk and protective factors at each stage.

Perspective.

Individuals at risk of GA or with GA.

Progression to GA and GA expansion rate.

Critical synthesis of the literature on risk and protective factors, both environmental and genetic, for progression to GA versus GA expansion in AMD.

Comparison of the risk and protective factors demonstrates partially overlapping but partially distinct risk and protective factors for progression to GA versus GA expansion. Some factors are shared (i.e., operating in the same direction at both stages), others are not shared, and others seem to operate in different directions at each stage. Risk variants at ARMS2/HTRA1 increase both risk of progression to GA and GA expansion rate, presumably through the same mechanism. By contrast, risk and protective variants at CFH/CFHR alter risk of GA but not GA expansion rate. A risk variant at C3 increases risk of GA but is associated with slower GA expansion. In environmental factors, cigarette smoking is associated with increased risk of GA and faster GA expansion, whereas increased age is associated with the former but not the latter. The Mediterranean diet is associated with decreased progression at both stages, although the food components with the largest contributions seem to differ between the 2 stages. Some phenotypic features, such as reticular pseudodrusen and hyperreflective foci, are associated with increased progression at both stages.

Analysis of the risk and protective factors for progression to GA and GA expansion demonstrates partially overlapping but partially distinct elements at each stage: some are shared, some are relevant to 1 stage only, and some even seem active in opposite directions at each stage. Aside from ARMS2/HTRA1, the overlap between the genetic risk factors for the 2 stages is minimal. This suggests that the biologic mechanisms differ at least partially between the 2 disease stages. This has implications for therapeutic approaches and suggests that treatment aimed at the underlying disease processes may need to be tailored by stage.

Proprietary or commercial disclosure may be found after the references.