Progression Of Age-related Macular Degeneration Research Articles

Melanophages give rise to hyperreflective foci in AMD, a disease-progression marker

Retinal melanosome/melanolipofuscin-containing cells (MCCs), clinically visible as hyperreflective foci (HRF) and a highly predictive imaging biomarker for the progression of age-related macular degeneration (AMD), are widely believed to be migrating retinal pigment epithelial (RPE) cells. Using human donor tissue, we identify the vast majority of MCCs as melanophages, melanosome/melanolipofuscin-laden mononuclear phagocytes (MPs). Using serial block-face scanning electron microscopy, RPE flatmounts, bone marrow transplantation and in vitro experiments, we show how retinal melanophages form by the transfer of melanosomes from the RPE to subretinal MPs when the “don’t eat me” signal CD47 is blocked. These melanophages give rise to hyperreflective foci in Cd47−/−-mice in vivo, and are associated with RPE dysmorphia similar to intermediate AMD. Finally, we show that Cd47 expression in human RPE declines with age and in AMD, which likely participates in melanophage formation and RPE decline. Boosting CD47 expression in AMD might protect RPE cells and delay AMD progression.

TRAP1 Is Expressed in Human Retinal Pigment Epithelial Cells and Is Required to Maintain their Energetic Status.

Age-related macular degeneration (AMD) is the leading cause of severe vision loss and blindness in elderly people worldwide. The damage to the retinal pigment epithelium (RPE) triggered by oxidative stress plays a central role in the onset and progression of AMD and results from the excessive accumulation of reactive oxygen species (ROS) produced mainly by mitochondria. Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial molecular chaperone that contributes to the maintenance of mitochondrial integrity by decreasing the production and accumulation of ROS. The present study aimed to evaluate the presence and the role of TRAP1 in the RPE. Here, we report that TRAP1 is expressed in human adult retinal pigment epithelial cells and is located mainly in the mitochondria. Exposure of RPE cells to hydrogen peroxide decreases the levels of TRAP1. Furthermore, TRAP1 silencing increases intracellular ROS production and decreases mitochondrial respiratory capacity without affecting cell proliferation. Together, these findings offer novel insights into TRAP1 functions in RPE cells, opening possibilities to develop new treatment options for AMD.

The Relationship between Dietary Calcium and Age-Related Macular Degeneration.

Mineral element supplements are widely used in the older adult population. However, little is known of their impact on the progression of age-related macular degeneration (ARMD). The aim of this study was to examine the association between dietary micronutrients and ARMD in older adults. We enrolled 5227 participants from the National Health and Nutrition Examination Survey (NHANES 2005-2008) in this cross-sectional study. ARMD was evaluated using an ophthalmic digital imaging system and digital camera. Mineral element consumption was collected using a 24-hour dietary recall. The association between mineral element use and the presence of ARMD was determined by multivariable logistic regression. After adjusting for relevant variables, dietary calcium was negatively associated with ARMD (OR: 680, 95%CI: 0.482-0.960). In contrast to dietary form, serum concentration of calcium was not associated with ARMD. Moreover, increased dietary calcium was associated with reduced ARMD (OR: 0.684, 95%CI: 0.468-1.000). A lower consumption of dietary calcium was significantly associated with a higher risk of ARMD. Further longitudinal studies are necessary to explore these findings.

Peran Karotenoid Sebagai Pencegahan Degenerasi Makula

Macular degeneration or often called Age-related Macular Degeneration (AMD) is a degenerative disease that attacks the center of vision in the retina, namely the macula. In an effort to prevent the progression of AMD, consuming antioxidants has been shown to inhibit the AMD development process. Although currently there is no definite number of AMD sufferers in Indonesia, it is estimated that the number of AMD sufferers will continue to increase. Carotenoids are one of the antioxidant compounds that have been shown to inhibit the development of macular degeneration. Carotenoids are divided into several classes, one of which is the xanthophyll class. Lutein and zeaxanthin compounds belong to the xanthophyll class. The content of lutein and zeaxanthin in body plasma has been shown to reduce the risk of macular diseases such as AMD. This study aims to determine the role of carotenoids as the prevention of macular degeneration. The method used is a literature review in the form of a narrative review. Search literature in the form of journals and textbooks through Google Scholar, PubMed, Science Direct, and Research Gate, indexed by Scopus, ISSN, national journals and international journals. The journals used were published in the last 5 years and books published in the last 10 years. The results of the analysis show that carotenoid antioxidants are proven to be able to act as a prevention of AMD by reducing oxidative stress. Carotenoids will quench free radicals, thereby preventing the occurrence of lipid peroxidation, and preventing the formation of AMD. Carotenoids also prevent damage mediated by exposure to blue light. Consumption of lutein and zeaxanthin can also reduce the expression of VEGF (vascular endothelial growth factor) in the retina so that it can inhibit the increase of VEGF. It can be concluded that carotenoid antioxidants can prevent the progression of macular degeneration.

Efficacy and Safety of Nutraceutical Support in Age-Related Macular Degeneration Patients

Purpose: to assess the possibilities of nutraceutical support in AREDS-3 category age-related macular degeneration (AMD) patients.Patients and methods. The study included 30 AREDS-3 category AMD patients (30 eyes) aged 69.2 ± 5.7 years (12 men, 18 women). As the ophthalmic nutraceutical, the biological active supplement was used, including vitamins E, B1, B2, B3, B9, B12, C, lutein, zeaxantin, lycopene, resveratrol, beta-carotene, coenzyme Q10, copper, zinc, selenium (Oftolik®; 1 capsule, 2 times a day). Follow-up period: 12–16 months (6–8 courses of therapy). All those observed underwent: standard ophthalmological examination; fundus photo registration (Nidek); OCT (Opto-Vue); OCT-angiography (Zeiss); possible systemic side effects registration. The main criterion for nutraceutical support effectiveness was stabilization of AMD manifestation. The significance of a possible increase in number and (or) size of drusen (with the AREDS-3 category), as well as the appearance of patients with AMD of the AREDS-4 category, was assessed using the Pearson γ2 test. An additional criterion was the maximum corrected visual acuity (MCVA) stabilization. The mean and its standard deviation (M ± s) were calculated, the significance of differences was assessed using the Wilcoxon’s T-test.Results. None of the eyes included in the study showed progression from the AMD AREDS-3 category to AREDS-4. In one eye (3.33 %), an increase in the number of drusen was recorded; in 29 eyes (96.67 %), the number and size of drusen remained stable. These changes were not statistically significant (γ2 = 1.017; p = 0.314; p > 0.05). MCVA during the follow-up period remained stable with a slight but statistically insignificant trend towards its increase (from 0.69 ± 0.096 to 0.71 ± 0.07; Temp = 165, p > 0.05). In all observed patients, the tolerability of ophthalmonutraceutical was good, no significant side effects were recorded.Conclusion. Nutraceutical support prevented the progression of AMD from AREDS-3 to AREDS-4 during follow-up of 12–16 months. In the vast majority of patients (96.67 %), manifestation of AMD within the AREDS-3 category remained stable. After 6-8 courses of therapy, no significant side effects of nutraceutical support were recorded.

Effect of the Mediterranean Diet on Progression of Dry Form of Age-related Macular Degeneration.

The aim of this study was to investigate the possible effect of the Mediterranean diet (Med Diet) on the progression of age-related macular degeneration (AMD) in patients with early or intermediate stages of dry AMD. The present study included 164 patients with early or intermediate dry AMD. Data collected included demographics, anthropometric data, ophthalmic and medical history. AMD progression was evaluated using patients' optical coherence tomography (OCT) and visual acuity. Using the MedDietScore, sample's attachment to Med Diet was evaluated, and distinguished into high and low. The association of supplement intake and adherence to Med Diet with AMD progression was investigated using logistic regression. Sample's mean age was 73±7.4 years. A positive correlation was found between dietary supplementation and slowing of AMD progression, as well as between high adherence to Med Diet and slowing of AMD progression. In contrast, smokers had 51.4% higher risk of AMD progression (p=0.043). The rate of slowing AMD progression was higher in patients who followed Med Diet and received a dietary supplement, compared to patients who followed one or none of the aforementioned recommendations (p<0.001). Adherence to the Med Diet could have a positive effect on delaying AMD progression in advanced stages, both in patients receiving or not antioxidants. Therefore, our study proposes to strengthen recommendations to AMD patients to follow a Med Diet.

The Noncanonical Role of Complement Factor H in Retinal Pigment Epithelium (RPE) Cells and Implications for Age-Related Macular Degeneration (AMD).

Age-related macular degeneration (AMD) is a complex degenerative disease of the retina. Dysfunction of the retinal pigment epithelium (RPE) occurs in early stages of AMD, and progressive RPE atrophy leads to photoreceptor death and visual impairments that ultimately manifest as geographic atrophy (GA), one of the late-stage forms of AMD. AMD is caused by a combination of risk factors including aging, lifestyle choices, and genetic predisposition. A gene variant in the complement factor H gene (CFH) that leads to the Y402H polymorphism in the factor H protein (FH) confers the second highest risk for the development and progression of AMD. FH is a major negative regulator of the alternative pathway of the complement system, and the FH Y402H variant leads to increased complement activation, which is detectable in AMD patients. For this reason, various therapeutic approaches targeting the complement system have been developed, however, so far with very limited or no efficacy. Interestingly, recent studies suggest roles for FH beyond complement regulation. Here, we will discuss the noncanonical functions of FH in RPE cells and highlight the potential implications of those functions for future therapeutic approaches.

Disturbed Matrix Metalloproteinases Activity in Age-Related Macular Degeneration.

Matrix metalloproteinases (MMPs) are a tightly regulated family of proteolytic enzymes that break down extracellular matrix (ECM) and basement membrane components. Because it is associated with development, morphogenesis, tissue remodeling, and repair, ECM remodeling is an important mechanism. MMPs are thought to act as a double-edged sword, as they contribute to maintaining photoreceptors/retinal pigment epithelium (RPE)/Bruch's membrane (BM)/choroid complex homeostasis and also contribute to the onset and progression of age-related macular degeneration (AMD). Polymorphisms and/or altered expression in MMPs and their tissue inhibitors (TIMPs) are associated with age-related macular degeneration (AMD). Here, we review the evidence for MMPs' role in the onset and progression of AMD via addressing their regulation and TIMPs' significant regulatory functions.

Oxidative stress in retinal pigment epithelium degeneration: from pathogenesis to therapeutic targets in dry age-related macular degeneration.

Age-related macular degeneration is a primary cause of blindness in the older adult population. Past decades of research in the pathophysiology of the disease have resulted in breakthroughs in the form of anti-vascular endothelial growth factor therapies against neovascular age-related macular degeneration; however, effective treatment is not yet available for geographical atrophy in dry age-related macular degeneration or for preventing the progression from early or mid to the late stage of age-related macular degeneration. Both clinical and experimental investigations involving human age-related macular degeneration retinas and animal models point towards the atrophic alterations in retinal pigment epithelium as a key feature in age-related macular degeneration progression. Retinal pigment epithelium cells are primarily responsible for cellular-structural maintenance and nutrition supply to keep photoreceptors healthy and functional. The retinal pigment epithelium constantly endures a highly oxidative environment that is balanced with a cascade of antioxidant enzyme systems regulated by nuclear factor erythroid-2-related factor 2 as a main redox sensing transcription factor. Aging and accumulated oxidative stress triggers retinal pigment epithelium dysfunction and eventually death. Exposure to both environmental and genetic factors aggravates oxidative stress damage in aging retinal pigment epithelium and accelerates retinal pigment epithelium degeneration in age-related macular degeneration pathophysiology. The present review summarizes the role of oxidative stress in retinal pigment epithelium degeneration, with potential impacts from both genetic and environmental factors in age-related macular degeneration development and progression. Potential strategies to counter retinal pigment epithelium damage and protect the retinal pigment epithelium through enhancing its antioxidant capacity are also discussed, focusing on existing antioxidant nutritional supplementation, and exploring nuclear factor erythroid-2-related factor 2 and its regulators including REV-ERBα as therapeutic targets to protect against age-related macular degeneration development and progression.

Untargeted Lipidomic Profiling of Aged Human Retina With and Without Age-Related Macular Degeneration (AMD).

The molecular characterization of extracellular deposits is crucial to understanding the clinical progression of AMD. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis is a powerful analytical discovery tool capable of identifying lipids in an untargeted manner. NanoLC-MS/MS is an analytical tool capable of identifying lipids with high sensitivity and minimum sample usage. Hence, the purpose of this study was to compare retina lipid identification from RPE-choroid samples using high flow LC-MS/MS and nanoLC-MS/MS. Manually dissected paraformaldehyde-fixed human donor tissues sections were used for LC-MS/MS and nanoLC-MS/MS analysis. Lipids were extracted with MeOH/MTBE/CHCl3 (MMC) and were analyzed by LC-MS/MS and nanoLC-MS/MS using negative and positive ionization modes. Untargeted lipidomics using LC-MS/MS identified 215 lipids from 4 lipid classes and 15 subclasses. We observed a 78% increase in lipid identifications using nanoLC-MS/MS with lipid numbers totaling 384. The nanoLC-MS/MS method is expected to provide extensive lipid identifications from small retina samples, e.g., from drusen and drusenoid deposits in aged and AMD eyes, and could help elucidate how lipids are involved in extracellular deposit formation in AMD.

Каротиноиды в терапии возрастной макулярной дегенерации: система доставки имеет значение

Age-related macular degeneration (AMD) is one of the leading causes of low vision and blindness worldwide for people over age 60. By 2040, the number of people living with macular degeneration is expected to reach 288 million due to the exponential acceleration of population aging. A decline in visual functions caused by AMD has a significant economic impact in all countries. Besides aging, there are other multiple heterogenic risk factors associated with AMD: gender, environmental condition, lifestyle, genetic characteristics, chronic inflammatory processes in the human body, level of education, etc. It is important for the ophthalmologist to be aware of modifiable risk factors and thus to collect a comprehensive medical history, interact with patients using motivational interviewing and to involve promptly other healthcare specialists into the patient management strategy. Etiopathogenesis of AMD is still not entirely understood. However, it is known that the major pathways include age-related alterations of retinal pigment epithelium (RPE) cells, oxidative stress, dysregulated lipid metabolism, inflammation, hemodynamic changes, and neovascularization. Carotenoids lutein and zeaxanthin are natural compounds with a proven efficacy in reducing AMD progression, which have been demonstrated to act as medications for patients with early AMD stages. The micro- encapsulated formula offers such an advantage as gradual and controlled release of active substances. Keywords: age-related macular degeneration, risk factors, etiopathogenesis, carotenoids, lutein, zeaxanthin, microcapsules. For citation: Maksimov M.L., Oganezova J.G., Kanner I.D., Voznesenskaya A.A. Carotenoids in the treatment of age-related macular degeneration: a drug delivery system does matter. Russian Journal of Clinical Ophthalmology. 2023;23(1):60–65 (in Russ.). DOI: 10.32364/2311-7729-2023-23-1-60-65.

Fluorescence Lifetime and Spectral Characteristics of Subretinal Drusenoid Deposits and Their Predictive Value for Progression of Age-Related Macular Degeneration.

To measure fundus autofluorescence (FAF) lifetimes and peak emission wavelengths (PEW) of subretinal drusenoid deposits (SDD) in age-related macular degeneration (AMD) and their development over time. Fluorescence lifetime imaging ophthalmoscopy (FLIO) was performed in 30 eyes with optical coherence tomography (OCT)-confirmed early or intermediate AMD and SDD. Contrasts of mean lifetimes in short- (SSC) and long-wavelength channels (LSC), PEW, and relative fluorescence intensity were determined as differences of the respective measures at individual SDD and their environment. Measurements were made at baseline and at follow-up intervals 1 (13-36 months) and 2 (37-72 months), respectively. Of 423 SDD found at baseline, 259, 47, and 117 were hypoautofluorescent, isoautofluorescent, and hyperautofluorescent, respectively. FAF lifetimes of SDD were significantly longer than those of their environment by 14.5 ps (SSC, 95% confidence interval [CI], 13.3-15.7 ps) and 3.9 ps (LSC, 3.1-4.7 ps). PEW was shorter by 1.53 nm (1.07-1.98 nm, all contrasts P < 0.001) with higher contrasts for hyperfluorescent SDD. Over follow-up, SDD tended to hyperautofluorescence (relative intensities increased by 3.4% [95% CI, 2.9%-4.1%; P < 0.001] in follow-up 2). Hyperautofluorescence was associated with disruption of the ellipsoid zone on OCT. Disease progression to late-stage AMD was associated with higher lifetime contrast in SSC (15.9ps [14.2-17.6 ps] vs. 11.7 ps [9.9-13.5 ps], P < 0.001) at baseline. SDD show longer FAF lifetimes and shorter PEW than their environments. A high lifetime contrast of SDD in SSC might predict disease progression to late-stage AMD.

Hyperpigmentary abnormalities in age-related macular degeneration: association with progression and impact on visual sensitivity

Background/aimsTo investigate the additional prognostic value of quantifying the extent of colour fundus photography (CFP)-defined hyperpigmentary abnormalities (HPAs) compared with their presence alone for predicting progression to late-stage age-related macular...

Association of Metformin With the Development of Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a leading cause of blindness with no treatment available for early stages. Retrospective studies have shown an association between metformin and reduced risk of AMD. To investigate the association between metformin use and age-related macular degeneration (AMD). The Diabetes Prevention Program Outcomes Study is a cross-sectional follow-up phase of a large multicenter randomized clinical trial, Diabetes Prevention Program (1996-2001), to investigate the association of treatment with metformin or an intensive lifestyle modification vs placebo with preventing the onset of type 2 diabetes in a population at high risk for developing diabetes. Participants with retinal imaging at a follow-up visit 16 years posttrial (2017-2019) were included. Analysis took place between October 2019 and May 2022. Participants were randomly distributed between 3 interventional arms: lifestyle, metformin, and placebo. Prevalence of AMD in the treatment arms. Of 1592 participants, 514 (32.3%) were in the lifestyle arm, 549 (34.5%) were in the metformin arm, and 529 (33.2%) were in the placebo arm. All 3 arms were balanced for baseline characteristics including age (mean [SD] age at randomization, 49 [9] years), sex (1128 [71%] male), race and ethnicity (784 [49%] White), smoking habits, body mass index, and education level. AMD was identified in 479 participants (30.1%); 229 (14.4%) had early AMD, 218 (13.7%) had intermediate AMD, and 32 (2.0%) had advanced AMD. There was no significant difference in the presence of AMD between the 3 groups: 152 (29.6%) in the lifestyle arm, 165 (30.2%) in the metformin arm, and 162 (30.7%) in the placebo arm. There was also no difference in the distribution of early, intermediate, and advanced AMD between the intervention groups. Mean duration of metformin use was similar for those with and without AMD (mean [SD], 8.0 [9.3] vs 8.5 [9.3] years; P = .69). In the multivariate models, history of smoking was associated with increased risks of AMD (odds ratio, 1.30; 95% CI, 1.05-1.61; P = .02). These data suggest neither metformin nor lifestyle changes initiated for diabetes prevention were associated with the risk of any AMD, with similar results for AMD severity. Duration of metformin use was also not associated with AMD. This analysis does not address the association of metformin with incidence or progression of AMD.

Bioprinted 3D outer retina barrier uncovers RPE-dependent choroidal phenotype in advanced macular degeneration.

Age-related macular degeneration (AMD), a leading cause of blindness, initiates in the outer-blood-retina-barrier (oBRB) formed by the retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris. The mechanisms of AMD initiation and progression remain poorly understood owing to the lack of physiologically relevant human oBRB models. To this end, we engineered a native-like three-dimensional (3D) oBRB tissue (3D-oBRB) by bioprinting endothelial cells, pericytes, and fibroblasts on the basal side of a biodegradable scaffold and establishing an RPE monolayer on top. In this 3D-oBRB model, a fully-polarized RPE monolayer provides barrier resistance, induces choriocapillaris fenestration, and supports the formation of Bruch's-membrane-like structure by inducing changes in gene expression in cells of the choroid. Complement activation in the 3D-oBRB triggers dry AMD phenotypes (including subRPE lipid-rich deposits called drusen and choriocapillaris degeneration), and HIF-α stabilization or STAT3 overactivation induce choriocapillaris neovascularization and type-I wet AMD phenotype. The 3D-oBRB provides a physiologically relevant model to studying RPE-choriocapillaris interactions under healthy and diseased conditions.

Retinal protection by fungal product theissenolactone B in a sodium iodate-induced AMD model through targeting retinal pigment epithelial matrix metalloproteinase-9 and microglia activity

Age-related macular degeneration (AMD) is the leading cause of low vision and blindness for which there is currently no cure. Increased matrix metalloproteinase-9 (MMP-9) was found in AMD and potently contributes to its pathogenesis. Resident microglia also promote the processes of chronic neuroinflammation, accelerating the progression of AMD. The present study investigates the effects and mechanisms of the natural compound theissenolactone B (LB53), isolated from Theissenia cinerea, on the effects of RPE dysregulation and microglia hyperactivation and its retinal protective ability in a sodium iodate (NaIO3)-induced retinal degeneration model of AMD. The fungal component LB53 significantly reduces MMP-9 gelatinolysis in TNF-α-stimulated human RPE cells (ARPE-19). Similarly, LB53 abolishes MMP-9 protein and mRNA expression in ARPE-19 cells. Moreover, LB53 efficiently suppresses nitric oxide (NO) production, iNOS expression, and intracellular ROS levels in LPS-stimulated TLR 4-activated microglial BV-2 cells. According to signaling studies, LB53 specifically targets canonical NF-κB signaling in both ARPE-19 and BV-2 microglia. In an RPE-BV-2 interaction assay, LB53 ameliorates LPS-activated BV-2 conditioned medium-induced MMP-9 activation and expression in the RPE. In NaIO3-induced AMD mouse model, LB53 restores photoreceptor and bipolar cell dysfunction as assessed by electroretinography (ERG). Additionally, LB53 prevents retinal thinning, primarily the photoreceptor, and reduces retinal blood flow from NaIO3 damage evaluated by optic coherence tomography (OCT) and laser speckle flowgraphy (LSFG), respectively. Our results demonstrate that LB53 exerts neuroprotection in a mouse model of AMD, which can be attributed to its anti-retinal inflammatory effects by impeding RPE-mediated MMP-9 activation and anti-microglia.

Pars plana vitrectomy for vitreoretinal interface disorders coincident with intermediate stage age-related macular degeneration.

Currently around 67 million people in Europe are affected by some form of age-related macular degeneration (AMD). As most known types of vitreoretinal (VR) interface disorders can coexist with AMD and as we can favourably affect the former with vitreoretinal surgery, our goal was to evaluate the results of vitreoretinal interface disorder surgery with macular peeling in relation to coincident intermediate stage AMD. This was a retrospective evaluation of eyes operated with 25-gauge pars plana vitrectomy (PPV). The monitored parameters were anatomical and functional findings and, safety of the procedure. The surface of the macula was stained with trypan blue and treated (peeling) with a disposable microforceps. 10% perfluoropropane, or the air tamponade was used. Distance visual acuity was examined on the ETDRS chart, the macular finding was monitored by OCT and photodocumented. The post-operative face-down position was 3-5 days. The follow-up period was 6 months. 17 eyes (14 patients, woman 86%) mean age 74 years. The primary indications for the procedure were: idiopathic macular hole (IMD) 59%, epiretinal membrane 29% and vitreomacular traction syndrome 12%. Ophthalmoscopic and OCT findings of intermediate dry form of AMD (100%), in 24% was drusoid ablation of the pigment leaf. In all cases of IMD, primary closure occurred. Input visual acuity 0.1-0.6 improved to 0.2-0.9 at the end of the follow-up period (P<0.05). No complications during surgery or progression of AMD in the follow-up period were observed. PPV for vitreoretinal interface disorders have similar anatomical results, whether the outer part of the retina is disrupted by intermediate AMD or not. Functional results are affected by possible disruption of the RPE or the outer layers of the neuroretina by AMD. The PPV procedure has a standard security profile. It is safe and does not affect the progression of AMD in the short term.

Prolonged Lifetimes of Histologic Autofluorescence in Ectopic Retinal Pigment Epithelium in Age-Related Macular Degeneration.

The purpose of this study was to investigate histologic autofluorescence lifetimes and spectra of retinal pigment epithelium (RPE) on the transition from normal aging to RPE activation and migration in age-related macular degeneration (AMD). Autofluorescence lifetimes and spectra of 9 donor eyes were analyzed in cryosections by means of 2-photon excited fluorescence at 960 nm. Spectra were detected at 483 to 665 nm. Lifetimes were measured using time-correlated single photon counting in 2 spectral channels: 500 to 550 nm (short-wavelength spectral channel [SSC]) and 550 to 700 nm (long-wavelength spectral channel [LSC]). Fluorescence decays over time were approximated by a series of three exponential functions. The amplitude-weighted mean fluorescence lifetime was determined. Markers for retinoid activity (RPE65) and immune function (CD68) were immunolocalized in selected neighboring sections. We identified 9 RPE morphology phenotypes resulting in 399 regions of interest (ROIs) for spectral and 497 ROIs for lifetime measurements. RPE dysmorphia results in a shorter wavelength peak of spectral emission: normal aging versus RPE migrated into the retina (intraELM) = 601.7 (9.5) nm versus 581.6 (7.3) nm, P < 0.001, whereas autofluorescence lifetimes increase: normal aging versus intraELM: SSC 180 (44) picosecond (ps) versus 320 (86) ps, P < 0.001; and LSC 250 (55) ps versus 441 (76) ps, P < 0.001. Ectopic RPE within the neurosensory retina is strongly CD68 positive and RPE65 negative. In the process of RPE degeneration, comprising different steps of dysmorphia and migration, lengthening of autofluorescence lifetimes and a hypsochromic shift of emission spectra can be observed. These autofluorescence changes might provide early biomarkers for AMD progression and contribute to our understanding of RPE-driven pathology.

Association of Nutrients, Specific Dietary Patterns, and Probiotics with Age-related Macular Degeneration.

Age-related macular degeneration (AMD) is a complex disease that mainly affects people over 50 years of age. Even though management of the vascularisation associated with the "wet" form of AMD is effective using anti-VEGF drugs, there is currently no treatment for the "dry" form of AMD. Given this, it is imperative to develop methods for disease prevention and treatment. For this review, we searched scientific articles via PubMed and Google Scholar, and considered the impact of nutrients, specific dietary patterns, and probiotics on the incidence and progression of AMD. Many studies revealed that regular consumption of foods that contain ω-3 fatty acids is associated with a lower risk for late AMD. Particular dietary patterns, such as the Mediterranean diet that contains ω-3 FAs-rich foods (nuts, olive oil, and fish), seem to be protective against AMD progression compared to Western diets that are rich in fats and carbohydrates. Furthermore, randomized controlled trials that investigated the role of nutrient supplementation in AMD have shown that treatment with antioxidants, such as lutein/zeaxanthin, zinc, and carotenoids, may be effective against AMD progression. More recent studies have investigated the association of the antioxidant properties of gut bacteria, such as Bacteroides and Eysipelotrichi, with lower AMD risk in individuals whose microbiota is enriched with them. These are promising fields of research that may yield the capacity to improve the quality of life for millions of people, allowing them to live with a clear vision for longer and avoiding the high cost of vision-saving surgery.

Does senescence play a role in age-related macular degeneration?

Advanced age is the most established risk factor for developing age-related macular degeneration (AMD), one of the leading causes of visual impairment in the elderly, in Western and developed countries. Similarly, after middle age, there is an exponential increase in pathologic molecular and cellular events that can induce senescence, traditionally defined as an irreversible loss of the cells' ability to divide and most recently reported to also occur in select post-mitotic and terminally differentiated cells, such as neurons. Together these facts raise the question as to whether or not cellular senescence, may play a role in the development of AMD. A number of studies have reported the effect of ocular-relevant inducers of senescence using primarily in vitro models of poorly polarized, actively dividing retinal pigment epithelial (RPE) cell lines. However, in interpretating the data, the fidelity of these culture models to the RPE in vivo, must be considered. Fewer studies have explored the presence and/or impact of senescent cells in in vivo models that present with phenotypic features of AMD, leaving this an open field for further investigation. The goal of this review is to discuss current thoughts on the potential role of senescence in AMD development and progression, with consideration of the model systems used and their relevance to human disease.