Age-related Retinal Diseases Research Articles

Leveraging Optical Coherence Tomography and Angiography Artifacts to Identify Clinicopathological Correlates in Macular Disorders

Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA) are pivotal imaging techniques in diagnosing and managing macular disorders, providing high-resolution cross-sectional images of the retina. Although OCT artifacts are often deemed undesirable, they can paradoxically offer valuable insights into retinal pathology. This review explores the potential of OCT and OCTA artifacts to serve as indicators of pathological correlates in various macular conditions. The study emphasizes the importance of recognizing and leveraging these artifacts to refine clinicopathologic correlates characterizing several macular disorders, including age-related macular degeneration, diabetic retinopathy, and retinal vascular occlusive disease. OCT artifacts can reflect the ultrastructure and composition of pathological features, and their recognition can thus expand the understanding of the pathogenesis and improve the diagnostic interpretation of macular disorders. With the widespread use of OCT and OCTA technologies, identifying artifacts with clinicopathologic significance is of paramount importance and may have significant implications for management and prognosis.

Serine and glycine physiology reversibly modulate retinal and peripheral nerve function

Metabolic homeostasis is maintained by redundant pathways to ensure adequate nutrient supply during fasting and other stresses. These pathways are regulated locally in tissues and systemically via the liver, kidney, and circulation. Here, we characterize how serine, glycine, and one-carbon (SGOC) metabolism fluxes across the eye, liver, and kidney sustain retinal amino acid levels and function. Individuals with macular telangiectasia (MacTel), an age-related retinal disease with reduced circulating serine and glycine, carrying deleterious alleles in SGOC metabolic enzymes exhibit an exaggerated reduction in circulating serine. A Phgdh+/- mouse model of this haploinsufficiency experiences accelerated retinal defects upon dietary serine/glycine restriction, highlighting how otherwise silent haploinsufficiencies can impact retinal health. We demonstrate that serine-associated retinopathy and peripheral neuropathy are reversible, as both are restored in mice upon serine supplementation. These data provide molecular insights into the genetic and metabolic drivers of neuro-retinal dysfunction while highlighting therapeutic opportunities to ameliorate this pathogenesis.

The Circadian Clock of Müller Glia Is Necessary for Retinal Homeostasis and Neuronal Survival

Biological processes throughout the body are orchestrated in time through the regulation of local circadian clocks. The retina is among the most metabolically active tissues, with demands depending greatly on the light/dark cycle. Most cell types within the retina are known to express the circadian clock in rodents; however, retinal clock expression in the human has not previously been localized. Moreover, the effect of local circadian clock dysfunction on retinal homeostasis is incompletely understood. We demonstrate an age-dependent decline in circadian clock gene and protein expression in the human retina. Using an animal model of targeted Bmal1 deficiency, we identify the circadian clock of the retinal Müller glia as essential for neuronal survival, vascular integrity, and retinal function. These results suggest a potential role for the local retinal circadian clock within the Müller glia in age-related retinal disease and retinal degeneration.

Применение витаминно-минерального комплекса у пациента с промежуточной стадией возрастной макулярной дегенерации и онкологической патологией в анамнезе

The use of the vitamin and mineral complex in a patient with an intermediate stage of age-related macular degeneration and concomitant oncological pathology A.I. Malakhova Smolensk Regional Clinical Hospital, Smolensk, Russian Federation Relevance. As life expectancy increases, the risks of developing age-related retinal diseases such as age-related macular degeneration (AMD) increase. Unfortunately, with increasing life expectancy, older patients are increasingly diagnosed with oncology, which is important to consider when managing patients with AMD. Purpose. To present a clinical example of a patient with an intermediate stage of age-related macular degeneration and a history of cancer, taking vitamin and mineral complexes containing lutein, zeaxanthin, antioxidants, and B vitamins in courses for 7 years. Methods. Patient Sh. born 1952 AMD in the intermediate stage of the disease was identified in 2017. There is a history of lung cancer. Results. At the first examination in 2017, «soft» drusen measuring 250–270 µm were detected on horizontal OCT sections. Over 7 years, there was no transition from intermediate to late stage AMD in the presence of high risk. Conclusion. Complex therapy of a patient with AMD and a history of cancer over the past 7 years with the additional recommendation of a course of taking the Visleya dietary supplement helped to stabilize the condition of the retina and the transition from the intermediate stage of AMD to the late stage of the disease, without negatively affecting the general condition of the patient. Key words: age-related macular degeneration, Visleya, vitamin and mineral complex, intermediate stage

Regulatory T cells limit age-associated retinal inflammation and neurodegeneration

BackgroundAgeing is the principal risk factor for retinal degenerative diseases, which are the commonest cause of blindness in the developed countries. These conditions include age-related macular degeneration or diabetic retinopathy. Regulatory T cells play a vital role in immunoregulation of the nervous system by limiting inflammation and tissue damage in health and disease. Because the retina was long-considered an immunoprivileged site, the precise contribution of regulatory T cells in retinal homeostasis and in age-related retinal diseases remains unknown.MethodsRegulatory T cells were selectively depleted in both young (2–4 months) and aged (18–23 months) FoxP3-DTR mice. We evaluated neuroretinal degeneration, gliosis, subretinal space phagocyte infiltration, and retinal pigmented epithelium morphology through immunofluorescence analysis. Subsequently, aged Treg depleted animals underwent adoptive transfer of both young and aged regulatory T cells from wild-type mice, and the resulting impact on neurodegeneration was assessed. Statistical analyses employed included the U-Mann Whitney test, and for comparisons involving more than two groups, 1-way ANOVA analysis followed by Bonferroni’s post hoc test.ResultsOur study shows that regulatory T cell elimination leads to retinal pigment epithelium cell dysmorphology and accumulation of phagocytes in the subretinal space of young and aged mice. However, only aged mice experience retinal neurodegeneration and gliosis. Surprisingly, adoptive transfer of young but not aged regulatory T cells reverse these changes.ConclusionOur findings demonstrate an essential role for regulatory T cells in maintaining age retinal homeostasis and preventing age-related neurodegeneration. This previously undescribed role of regulatory T cells in limiting retinal inflammation, RPE/choroid epithelium damage and subsequently photoreceptor loss with age, opens novel avenues to explore regulatory T cell neuroprotective and anti-inflammatory properties as potential therapeutic approaches for age-related retinal diseases.

Roles of transmembrane protein 135 in mitochondrial and peroxisomal functions - implications for age-related retinal disease.

Aging is the most significant risk factor for age-related diseases in general, which is true for age-related diseases in the eye including age-related macular degeneration (AMD). Therefore, in order to identify potential therapeutic targets for these diseases, it is crucial to understand the normal aging process and how its mis-regulation could cause age-related diseases at the molecular level. Recently, abnormal lipid metabolism has emerged as one major aspect of age-related symptoms in the retina. Animal models provide excellent means to identify and study factors that regulate lipid metabolism in relation to age-related symptoms. Central to this review is the role of transmembrane protein 135 (TMEM135) in the retina. TMEM135 was identified through the characterization of a mutant mouse strain exhibiting accelerated retinal aging and positional cloning of the responsible mutation within the gene, indicating the crucial role of TMEM135 in regulating the normal aging process in the retina. Over the past decade, the molecular functions of TMEM135 have been explored in various models and tissues, providing insights into the regulation of metabolism, particularly lipid metabolism, through its action in multiple organelles. Studies indicated that TMEM135 is a significant regulator of peroxisomes, mitochondria, and their interaction. Here, we provide an overview of the molecular functions of TMEM135 which is crucial for regulating mitochondria, peroxisomes, and lipids. The review also discusses the age-dependent phenotypes in mice with TMEM135 perturbations, emphasizing the importance of a balanced TMEM135 function for the health of the retina and other tissues including the heart, liver, and adipose tissue. Finally, we explore the potential roles of TMEM135 in human age-related retinal diseases, connecting its functions to the pathobiology of AMD.

Microglia depletion/repopulation does not affect light-induced retinal degeneration in mice.

Reactive microglia are a hallmark of age-related retinal degenerative diseases including age-related macular degeneration (AMD). These cells are capable of secreting neurotoxic substances that may aggravate inflammation that leads to loss of photoreceptors and impaired vision. Despite their role in driving detrimental inflammation, microglia also play supporting roles in the retina as they are a crucial cellular component of the regulatory innate immune system. In this study, we used the colony stimulating factor 1 receptor (CSF1R)-antagonist PLX3397 to investigate the effects of microglia depletion and repopulation in a mouse model of acute retinal degeneration that mimics some aspects of dry AMD. Our main goal was to investigate whether microglia depletion and repopulation affects the outcome of light-induced retinal degeneration. We found that microglia depletion effectively decreased the expression of several key pro-inflammatory factors but was unable to influence the extent of retinal degeneration as determined by optical coherence tomography (OCT) and histology. Interestingly, we found prominent cell debris accumulation in the outer retina under conditions of microglia depletion, presumably due to the lack of efficient phagocytosis that could not be compensated by the retinal pigment epithelium. Moreover, our in vivo experiments showed that renewal of retinal microglia by repopulation did also not prevent rapid microglia activation or preserve photoreceptor death under conditions of light damage. We conclude that microglia ablation strongly reduces the expression of pro-inflammatory factors but cannot prevent photoreceptor loss in the light-damage paradigm of retinal degeneration.

Clinical evaluation of deep learning systems for assisting in the diagnosis of the epiretinal membrane grade in general ophthalmologists.

Epiretinal membrane (ERM) is a common age-related retinal disease detected by optical coherence tomography (OCT), with a prevalence of 34.1% among people over 60 years old. This study aims to develop artificial intelligence (AI) systems to assist in the diagnosis of ERM grade using OCT images and to clinically evaluate the potential benefits and risks of our AI systems with a comparative experiment. A segmentation deep learning (DL) model that segments retinal features associated with ERM severity and a classification DL model that grades the severity of ERM were developed based on an OCT dataset obtained from three hospitals. A comparative experiment was conducted to compare the performance of four general ophthalmologists with and without assistance from the AI in diagnosing ERM severity. The segmentation network had a pixel accuracy (PA) of 0.980 and a mean intersection over union (MIoU) of 0.873, while the six-classification network had a total accuracy of 81.3%. The diagnostic accuracy scores of the four ophthalmologists increased with AI assistance from 81.7%, 80.7%, 78.0%, and 80.7% to 87.7%, 86.7%, 89.0%, and 91.3%, respectively, while the corresponding time expenditures were reduced. The specific results of the study as well as the misinterpretations of the AI systems were analysed. Through our comparative experiment, the AI systems proved to be valuable references for medical diagnosis and demonstrated the potential to accelerate clinical workflows. Systematic efforts are needed to ensure the safe and rapid integration of AI systems into ophthalmic practice.

Polarized Desmosome and Hemidesmosome Shedding via Small Extracellular Vesicles is an Early Indicator of Outer Blood-Retina Barrier Dysfunction.

The retinal pigmented epithelium (RPE) constitutes the outer blood-retinal barrier, enables photoreceptor function of the eye, and is constantly exposed to oxidative stress. As such, dysfunction of the RPE underlies pathology leading to development of age-related macular degeneration (AMD), the leading cause of vision loss among the elderly in industrialized nations. A major responsibility of the RPE is to process photoreceptor outer segments, which relies on the proper functioning of its endocytic pathways and endosomal trafficking. Exosomes and other extracellular vesicles (EVs) from RPE are an essential part of these pathways and may be early indicators of cellular stress. To test the role of small EVs (sEVs) including exosomes, that may underlie the early stages of AMD, we used a polarized primary RPE cell culture model under chronic subtoxic oxidative stress. Unbiased proteomic analyses of highly purified basolateral sEVs from oxidatively stressed RPE cultures revealed changes in proteins involved in epithelial barrier integrity. There were also significant changes in proteins accumulating in the basal-side sub-RPE extracellular matrix during oxidative stress, that could be prevented with an inhibitor of sEV release. Thus, chronic subtoxic oxidative stress in primary RPE cultures induces changes in sEV content, including basal-side specific desmosome and hemidesmosome shedding via sEVs. These findings provide novel biomarkers of early cellular dysfunction and opportunity for therapeutic intervention in age-related retinal diseases (e.g., AMD).

Excessive Thyroid Hormone Signaling Induces Photoreceptor Degeneration in Mice.

Rod and cone photoreceptors degenerate in inherited and age-related retinal degenerative diseases, ultimately leading to loss of vision. Thyroid hormone (TH) signaling regulates cell proliferation, differentiation, and metabolism. Recent studies have shown a link between TH signaling and retinal degeneration. This work investigates the effects of excessive TH signaling on photoreceptor function and survival in mice. C57BL/6, Thra1 -/-, Thrb2 -/-, Thrb -/-, and the cone dominant Nrl -/- mice received triiodothyronine (T3) treatment (5-20 μg/ml in drinking water) for 30 d, followed by evaluations of retinal function, photoreceptor survival/death, and retinal stress/damage. Treatment with T3 reduced light responses of rods and cones by 50-60%, compared with untreated controls. Outer nuclear layer thickness and cone density were reduced by ∼18% and 75%, respectively, after T3 treatment. Retinal sections prepared from T3-treated mice showed significantly increased numbers of TUNEL-positive, p-γH2AX-positive, and 8-OHdG-positive cells, and activation of Müller glial cells. Gene expression analysis revealed upregulation of the genes involved in oxidative stress, necroptosis, and inflammation after T3 treatment. Deletion of Thra1 prevented T3-induced degeneration of rods but not cones, whereas deletion of Thrb2 preserved both rods and cones. Treatment with an antioxidant partially preserved photoreceptors and reduced retinal stress responses. This study demonstrates that excessive TH signaling induces oxidative stress/damage and necroptosis, induces photoreceptor degeneration, and impairs retinal function. The findings provide insights into the role of TH signaling in retinal degeneration and support the view of targeting TH signaling for photoreceptor protection.

Klotho prevents transforming growth factor-β2-induced senescent-like morphological changes in the retinal pigment epithelium

Degenerative changes of the retinal pigment epithelium (RPE) triggered by transforming growth factor-β2 (TGF-β2) and oxidative stress play a critical role in the progression of age-related macular degeneration (AMD). The expression of α-klotho, an antiaging protein, declines with age, increasing the risk factors for age-related diseases. Here, we investigated the protective effects of soluble α-klotho on TGF-β2-induced RPE degeneration. The morphological changes induced by TGF-β2, including epithelial-mesenchymal transition (EMT), were attenuated in the mouse RPE by the intravitreal injection (IVT) of α-klotho. In ARPE19 cells, EMT and morphological alterations by TGF-β2 were attenuated by co-incubation with α-klotho. TGF-β2 decreased miR-200a accompanied by zinc finger e-box binding homeobox1 (ZEB1) upregulation and EMT, all of which were prevented by α-klotho co-treatment. Inhibitor of miR-200a mimicked TGF-β2-induced morphological changes, which were recovered by ZEP1 silencing, but not by α-klotho, implying the upstream regulation of α-klotho on miR-200a-ZEP1-EMT axis. α-Klotho inhibited receptor binding of TGF-β2, Smad2/3 phosphorylation, extracellular signal-regulated protein kinase 1/2 (ERK1/2)-a mechanistic target of rapamycin (mTOR) activation and oxidative stress via NADPH oxidase 4 (NOX4) upregulation. Furthermore, α-klotho recovered the TGF-β2-induced mitochondrial activation and superoxide generation. Interestingly, TGF-β2 upregulated α-klotho expression in the RPE cells, and genetic suppression of endogenous α-klotho aggravated TGF-β2-induced oxidative stress and EMT. Lastly, α-klotho abrogated senescence-associated signaling molecules and phenotypes induced by long-term incubation with TGF-β2. Hence, our findings indicate that the antiaging α-klotho plays a protective role against EMT and degeneration of the RPE, demonstrating the therapeutic potential for age-related retinal diseases, including the dry type of AMD.

DAPL1 deficiency in mice impairs antioxidant defenses in the RPE and leads to retinal degeneration with AMD-like features

The decreased antioxidant capacity in the retinal pigment epithelium (RPE) is the hallmark of retinal degenerative diseases including age-related macular degeneration (AMD). Nevertheless, the exact regulatory mechanisms underlying the pathogenesis of retinal degenerations remain largely unknown. Here we show in mice that deficiencies in Dapl1, a susceptibility gene for human AMD, impair the antioxidant capacity of the RPE and lead to age-related retinal degeneration in the 18-month-old mice homozygous for a partial deletion of Dapl1. Dapl1-deficiency is associated with a reduction of the RPE's antioxidant capacity, and experimental re-expression of Dapl1 reverses this reduction and protects the retina from oxidative damage. Mechanistically, DAPL1 directly binds the transcription factor E2F4 and inhibits the expression of MYC, leading to upregulation of the transcription factor MITF and its targets NRF2 and PGC1α, both of which regulate the RPE's antioxidant function. When MITF is experimentally overexpressed in the RPE of DAPL1 deficient mice, antioxidation is restored and retinas are protected from degeneration. These findings suggest that the DAPL1-MITF axis functions as a novel regulator of the antioxidant defense system of the RPE and may play a critical role in the pathogenesis of age-related retinal degenerative diseases.

Prevalence of Diabetic Retinopathy in the City of Sarajevo, Bosnia and Herzegovina

Background: The main causes of severe vision loss and blindness in Europe are age-related retinal diseases, particularly age-related macular degeneration (AMD), diabetic eye disease (DED), and a host of vascular conditions. Both the prevalence and incidence of severe vision loss are expected to increase in territories where life expectancy is increasing. Objective: The aim of this study is to estimate the current prevalence of diabetic retinopathy and the most common risks for its development in the city of Sarajevo, a Capital of Bosnia and Herzegovina. Methods: This retrospective single center study included 205 diabetic patients from the city of Sarajevo who attended the regular ophthalmological examination at the Specialty Eye Hospital Svjetlost, in a branch located in the city center, from August 2021 to August 2022. Patients underwent a complete medical assessment by ophthalmology specialists. The retinal examination included an evaluation of the presence of diabetic retinopathy. Any retinopathy present was graded as mild non-proliferative retinopathy, moderate-severe non-proliferative retinopathy, or proliferative retinopathy (PDR). Results: Retinopathy was present in 40.49 % of patients included in this study; 13.17 % had the mild form of diabetic retinopathy, 7.80 % had the moderate-severe form, and 19.51 % had a proliferative form of diabetic retinopathy. The mean duration of diabetes diagnosis was 11.12 years overall, 11.74 years in men, and 10.22 in women. Macular edema was present in 38.55% of patients with retinopathy, 6.02 % in patients with mild form, 8.43 % in patients with moderate-severe form, and 24.09 % in patients with PDR. Conclusion: The prevalence of diabetic retinopathy in Sarajevo is relatively high, and the most common is a severe form of the disease. Regular diabetic retinopathy screening in primary healthcare services and hospital eye services is highly recommended for the timely prevention of visual impairment and blindness.

Isozyme-specific histone deacetylase 1/2 inhibitor K560 attenuates oxidative stress-induced retinal cell death

Oxidative stress-induced damage is an underlying mechanism in the pathogenesis of age-related retinal diseases. Here, we examined the effects of K560, a potential candidate drug for the treatment of these diseases, on oxidative stress-induced retinal cell death. K560 is a novel isozyme-specific inhibitor of histone deacetylase 1 and 2 (HDAC1/2). Histone acetylation in retinal lysates and dissociated retinal cells was detected with a western blot analysis and cell-based enzyme-linked immunosorbent assay (ELISA), respectively. The viability of mouse retinal cells was measured with an alamarBlue assay. We used immunohistochemistry for RNA binding protein with multiple splicing (RBPMS) to visualize the retinal ganglion cells (RGCs) of mice. An ELISA analysis indicated that histone acetylation was enhanced in dissociated mouse retinal cells treated with K560. The cell viability assay indicated that K560 attenuated both exogenous hydrogen peroxide–induced and endogenous oxidative stress–induced cell death in dissociated retinal cells. Western blot analysis indicated that intravitreal K560 administration enhanced the acetylation of histones H3 and H4 in mouse retinal lysates. To examine the effect of K560 on oxidative stress–induced RGC death, we performed whole-mount immunohistochemistry for RBPMS on retinas dissected from eyes treated with K560 or vehicle on day one, and K560 or vehicle and NMDA on day two. Quantification of RBPMS-immunopositive cells indicated that K560 attenuated NMDA-induced RGC death. Taken together, our findings suggest that administration of a HDAC1/2-specific inhibitor K560 may be effective in the treatment of oxidative stress–mediated retinal degeneration and have less cytotoxicity than other known HDAC inhibitors, which are known to target a wide range of HDAC family members.

The effect of a chrysanthemum water extract in protecting the retina of mice from light damage

BackgroundOxidative stress can induce age-related diseases. Age-related retinal diseases, such as age-related macular degeneration (AMD), are difficult to cure owing to their complicated mechanisms. Although anti-neovascular therapeutics are used to treat wet AMD, vision cannot always be completely restored, and disease progression cannot always be inhibited. Therefore, determining a method to prevent or slow retinal damage is important. This study aimed to investigate the protective effect of a chrysanthemum water extract rich in flavone on the oxidatively stressed retina of mice.MethodsLight damage was induced to establish oxidative stress mouse models. For in vitro experiments, ARPE-19 cells were cultured and divided into four groups: control, light-damaged, and low- and high-dose chrysanthemum extract. No treatment was administered in the control group. The light-damaged and low- and high-dose chrysanthemum extract groups were exposed to a similar white light level. The chrysanthemum extract was added at a low dose of 0.4 mg/mL or a high dose of 1.0 mg/mL before cell exposure to 2500-lx white light. Reactive oxygen species (ROS) level and cellular viability were measured using MTT and immunofluorescence staining. For in vivo experiments, C57BL/6 J mice were divided into the same four groups. Low- (0.23 g/kg/day) and high-dose (0.38 g/kg/day) chrysanthemum extracts were continuously intragastrically administered for 8 weeks before mouse exposure to 10,000-lx white light. Retinal function was evaluated using electroretinography. In vivo optical coherence tomography and in vitro haematoxylin and eosin staining were performed to observe the pathological retinal changes in each group after light damage. Fluorescein fundus angiography of the arteriovenous vessel was performed, and the findings were analysed using the AngioTool software. TUNEL immunofluorescence staining was used to assess isolated retinal apoptosis.ResultsIn vitro, increased ROS production and decreased ARPE-19 cell viability were found in the light-damaged group. Improved ARPE-19 cell viability and reduced ROS levels were observed in the chrysanthemum extract treatment groups. In vivo, dysfunctional retinas and abnormal retinal structures were found in the light-damaged group, as well as increased apoptosis in the retinal ganglion cells (RGCs) and inner and outer nuclear layers. The apoptosis rate in the same layers was lower in the chrysanthemum extract treatment groups than in the light-damaged group. The production of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), increased in the treatment groups. NF-κB in the nucleus and TNF-α were more highly expressed in the light-damaged group than in the low- and high-dose chrysanthemum extract groups.ConclusionsLight damage-induced retinal oxidative stress can lead to ROS accumulation in the retinal tissues. Herein, RGC and photoreceptor layer apoptosis was triggered, and NF-κB in the nucleus and TNF-α were highly expressed in the light-damaged group. Preventive chrysanthemum extract administration decreased ROS production by increasing SOD, CAT, and GSH-Px activities and reversing the negative changes, demonstrating a potential protective effect on the retina.

Distinctive features of eye pathology in elderly and senile people in Arkhangelsk region

Purpose: to identify the features of the pathology of the eye in elderly and senile people in the Arkhangelsk region. Material and methods. Annual reports of medical eye care facilities for the 2009 to 2019 who offered ophthalmological assistance to individuals aged 60 or older were analyzed. To estimate the differences infrequency of occurrence Pearson's Chi-square was used. Results. The incidence of eye pathologies in elderly and senile people amounts to 20.74% (17.83 % male and 22.29 % female). The most common conditions included the pathology of the lens that occurred in almost 50 % of the old people, glaucoma was diagnosed in about 20 % and retinal conditions in one out of seven people. In the age group of 60 to 74 years, the most common pathologies included glaucoma, diabetic angioretinopathy, retinal conditions and refractive errors; in the people of advanced age (75—89 years), lens pathologies and age-related macular degeneration occurred more frequently than in the younger age group while glaucoma, diabetic angioretinopathy, retinal conditions and refractive errors occurred less frequently. The oldest age group (90 years and older) showed a different pathology distribution than people of the younger age groups: they have higher occurrence of lens pathologies, age-related macular degeneration, optic disc pathology. In contrast, they have a rarer occurrence of retinal diseases, whilst diabetic angioretinopathy or refractive errors were not diagnosed at all. Gender differences of eye pathology distribution are revealed in the fact that, among people aged 60 to 89, women have a higher occurrence of age-related macular degeneration, retinal diseases and refractive errors, while men are more often diagnosed with glaucoma. Conclusion. The identified features of eye pathology in elderly and senile people living in the Arkhangelsk region should be taken into account when medical care for advanced age groups is developed and improved.

Glucose uptake by GLUT1 in photoreceptors is essential for outer segment renewal and rod photoreceptor survival.

Photoreceptors consume glucose supplied by the choriocapillaris to support phototransduction and outer segment (OS) renewal. Reduced glucose supply underlies photoreceptor cell death in inherited retinal degeneration and age-related retinal disease. We have previously shown that restricting glucose transport into the outer retina by conditional deletion of Slc2a1 encoding GLUT1 resulted in photoreceptor loss and impaired OS renewal. However, retinal neurons, glia, and the retinal pigment epithelium play specialized, synergistic roles in metabolite supply and exchange, and the cell-specific map of glucose uptake and utilization in the retina is incomplete. In these studies, we conditionally deleted Slc2a1 in a pan-retinal or rod-specific manner to better understand how glucose is utilized in the retina. Using non-invasive ocular imaging, electroretinography, and histochemical and biochemical analyses we show that genetic deletion of Slc2a1 from retinal neurons and Müller glia results in reduced OS growth and progressive rod but not cone photoreceptor cell death. Rhodopsin levels were severely decreased even at postnatal day 20 when OS length was relatively normal. Arrestin levels were not changed suggesting that glucose uptake is required to synthesize membrane glycoproteins. Rod-specific deletion of Slc2a1 resulted in similar changes in OS length and rod photoreceptor cell death. These studies demonstrate that glucose is an essential carbon source for rod photoreceptor cell OS maintenance and viability.

Sociodemographic predictors associated with the spectrum of non-opportunist neuroretinal disease of non-infectious etiology in patients with HIV/AIDS: A scoping review.

Non-infectious retinal disease, even in the HAART era, continues to be one of the most common diagnoses in patients with HIV, with prevalences of up to 27% of cases. This study aims to characterize the association between demographic variables and their role. As a risk factor for the development of non-opportunistic non-infectious retinal disease in patients with HIV/AIDS. An integrative review of the literature was carried out according to Arksey O'Malley's approach, based on the PICO methodology and following the PRISMA recommendations; An exhaustive search was carried out in databases of articles that were filtered using established criteria, with their extraction and analysis carried out qualitatively. Ocular manifestations from any cause develop from 35 years of age in patients with HIV/AIDS, with the highest risk for age-related macular degeneration over the fourth decade of life and for the development of neuroretinal disorder on the fifth decade of life; some studies report a slight tendency to diagnose macular degeneration in women and those who acquired AIDS through sexual contact; data contrasted with increased risk for diagnosing neuroretinal disorder in homosexual men who also use intravenous drugs, possibly due to oversampling in studies; non-Hispanic whites and African Americans were the races most commonly affected by neuroretinal disease; the means between the 11.3-14.5 years elapsed since the HIV diagnosis were more frequently associated with cognitive impairment and both in those with high or low CD4 counts, and in patients with high or low viral loads, neuroretinal disease without Statistically significant differences. Adherence and early initiation of HAART had a modest impact on the development of neuroretinal disease. Even in the HAART era, non-infectious neuroretinal disease and cytomegalovirus retinitis remain the most frequent ocular diagnoses, however, different studies argue an increase in age-related non-infectious retinal diseases in patients with HIV, theories that are may explain by the increase in life expectancy, the metabolic effects of HAART itself or the generalized pro-inflammatory state in this group of patients, it is essential to recognize this new diagnostic challenge in order to direct preventive efforts through the use of cost-effective sociodemographic risk predictors towards that technological tools for diagnosis and treatment can be targeted. HIV/AIDS patients who present at the ophthalmological consultation with the suggested sociodemographic predictors have a high risk of visual impairment due to non-infectious retinopathy, therefore prevention, diagnosis and treatment efforts directed at these diseases should be increased.

A mutation in transmembrane protein 135 impairs lipid metabolism in mouse eyecups

Aging is a significant factor in the development of age-related diseases but how aging disrupts cellular homeostasis to cause age-related retinal disease is unknown. Here, we further our studies on transmembrane protein 135 (Tmem135), a gene involved in retinal aging, by examining the transcriptomic profiles of wild-type, heterozygous and homozygous Tmem135 mutant posterior eyecup samples through RNA sequencing (RNA-Seq). We found significant gene expression changes in both heterozygous and homozygous Tmem135 mutant mouse eyecups that correlate with visual function deficits. Further analysis revealed that expression of many genes involved in lipid metabolism are changed due to the Tmem135 mutation. Consistent with these changes, we found increased lipid accumulation in mutant Tmem135 eyecup samples. Since mutant Tmem135 mice have similar ocular pathologies as human age-related macular degeneration (AMD) eyes, we compared our homozygous Tmem135 mutant eyecup RNA-Seq dataset with transcriptomic datasets of human AMD donor eyes. We found similar changes in genes involved in lipid metabolism between the homozygous Tmem135 mutant eyecups and AMD donor eyes. Our study suggests that the Tmem135 mutation affects lipid metabolism as similarly observed in human AMD eyes, thus Tmem135 mutant mice can serve as a good model for the role of dysregulated lipid metabolism in AMD.

Intraocular iron injection induces oxidative stress followed by elements of geographic atrophy and sympathetic ophthalmia

Iron has been implicated in the pathogenesis of age‐related retinal diseases, including age‐related macular degeneration (AMD). Previous work showed that intravitreal (IVT) injection of iron induces acute photoreceptor death, lipid peroxidation, and autofluorescence (AF). Herein, we extend this work, finding surprising chronic features of the model: geographic atrophy and sympathetic ophthalmia. We provide new mechanistic insights derived from focal AF in the photoreceptors, quantification of bisretinoids, and localization of carboxyethyl pyrrole, an oxidized adduct of docosahexaenoic acid associated with AMD. In mice given IVT ferric ammonium citrate (FAC), RPE died in patches that slowly expanded at their borders, like human geographic atrophy. There was green AF in the photoreceptor ellipsoid, a mitochondria‐rich region, 4 h after injection, followed later by gold AF in rod outer segments, RPE and subretinal myeloid cells. The green AF signature is consistent with flavin adenine dinucleotide, while measured increases in the bisretinoid all‐trans‐retinal dimer are consistent with the gold AF. FAC induced formation carboxyethyl pyrrole accumulation first in photoreceptors, then in RPE and myeloid cells. Quantitative PCR on neural retina and RPE indicated antioxidant upregulation and inflammation. Unexpectedly, reminiscent of sympathetic ophthalmia, autofluorescent myeloid cells containing abundant iron infiltrated the saline‐injected fellow eyes only if the contralateral eye had received IVT FAC. These findings provide mechanistic insights into the potential toxicity caused by AMD‐associated retinal iron accumulation. The mouse model will be useful for testing antioxidants, iron chelators, ferroptosis inhibitors, anti‐inflammatory medications, and choroidal neovascularization inhibitors.