Age-related decreases in autophagy contribute to the progression of age-related macular degeneration (AMD). We have now studied the interaction between autophagy impaired in retinal pigment epithelium (RPE) and the responses of macrophages. We find that dying RPE cells can activate the macrophage inflammasome and promote angiogenesis. In vitro, inhibiting rotenone-induced autophagy in RPE cells elicits caspase-3 mediated cell death. Co-culture of damaged RPE with macrophages leads to the secretion of IL-1β, IL-6 and nitrite oxide. Exogenous IL-6 protects the dysfunctional RPE but IL-1β causes enhanced cell death. Furthermore, IL-1β toxicity is more pronounced in dysfunctional RPE cells showing reduced IRAK3 gene expression. Co-culture of macrophages with damaged RPE also elicits elevated levels of pro-angiogenic proteins that promote ex vivo choroidal vessel sprouting. In vivo, impaired autophagy in the eye promotes photoreceptor and RPE degeneration and recruitment of inflammasome-activated macrophages. The degenerative tissue environment drives an enhanced pro-angiogenic response, demonstrated by increased size of laser-induced choroidal neovascularization (CNV) lesions. The contribution of macrophages was confirmed by depletion of CCR2+ monocytes, which attenuates CNV in the presence of RPE degeneration. Our results suggest that the interplay between perturbed RPE homeostasis and activated macrophages influences key features of AMD development.
Age‐related macular degeneration (AMD) is the leading cause of central vision loss worldwide. Loss of retinal pigment epithelium (RPE) is a major pathological hallmark in AMD with or without pathological neovascularization. Although activation of the immune system is implicated in disease progression, pathological pathways remain diverse and unclear. Here, we report an unexpected protective role of a pro‐inflammatory cytokine, interleukin‐33 (IL‐33), in ocular angiogenesis. IL‐33 and its receptor (ST2) are expressed constitutively in human and murine retina and choroid. When RPE was activated, IL‐33 expression was markedly elevated in vitro. We found that IL‐33 regulated tissue remodelling by attenuating wound‐healing responses, including reduction in the migration of choroidal fibroblasts and retinal microvascular endothelial cells, and inhibition of collagen gel contraction. In vivo, local administration of recombinant IL‐33 inhibited murine choroidal neovascularization (CNV) formation, a surrogate of human neovascular AMD, and this effect was ST2‐dependent. Collectively, these data demonstrate IL‐33 as a potential immunotherapy and distinguishes pathways for subverting AMD pathology. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
Photoreceptor apoptosis is a major cause of vision loss in many ocular diseases. Significant progress has been made to elucidate the molecular pathways involved in this process, yet little is known about proteins counteracting these apoptotic pathways. It is established that heat shock proteins (HSPs) function as molecular helper proteins (chaperones) by preventing protein aggregation and facilitating refolding of dysfunctional proteins, critical to the survival of all organisms. Here, we investigated the role of HSP70 on photoreceptor survival after experimental retinal detachment (RD) in mice and rats. We found that HSP70 was up-regulated after RD and associated with phosphorylated Akt, thereby preventing its dephosphorylation and further activation of cell death pathways. Administration of quercetin, which inhibits HSP70 and suppresses Akt phosphorylation significantly increased photoreceptor apoptosis. Similarly, RD-induced photoreceptor apoptosis was augmented in mice carrying hypomorphic mutations of the genes encoding HSP70. On the other hand, administration of geranylgeranylacetone, which induces an increase in HSP70 significantly decreased photoreceptor apoptosis after RD through prolonged activation of Akt pathway. Thus, HSP70 may be a favorable potential target to increase photoreceptor cell survival after RD.
ABSTRACT.Purpose: We conducted a case-control study to identify risk factors for cataract in the Mediterranean Greek population. Three hundred and fourteen cases and 314 frequency-matched controls of both genders, aged 45-85, attending the ophthalmology department of a major teaching hospital in Athens, Greece, were included in the study. Methods: Cases were medically diagnosed and classified. Controls were healthy visitors without cataract. A detailed questionnaire, covering demographic, socioeconomic, somatometric, lifestyle and medical history variables, provided data on possible risk factors for cataract. Analyses were conducted through multiple logistic regression. Main outcome measures: Cataract overall and by type: nuclear, cortical and posterior subcapsular (PSC). Results: Statistically significant increased risk for cataract overall was found for current (OR = 1.99, 95%CI: 1.23-3.23) and ex-smokers (OR = 1.64, 95%CI: 1.02-2.70), history of coronary heart disease (OR = 2.25, 95%CI: 1.43-3.55), family history of ophthalmologic diseases (OR = 1.51, 95%CI: 1.03-2.20) and higher sunlight exposure at the beach (OR = 2.26, 95%CI: 1.37-3.72) as well as at work (OR = 2.03, 95%CI: 1.32-3.12). Use of measures protecting against sunlight at the beach, i.e. hat (OR = 0.58, 95%CI: 0.39-0.85) and vision repair spectacles (OR = 0.44, 95%CI: 0.30-0.65), were associated with reduced risk. Results for cataract overall were also evident for the nuclear type and in most circumstances for PSC type, but were only suggestive for the cortical type of cataract. Conclusion: We identified certain possible risk factors for age-related cataract. In a Mediterranean Greek population, we found that smoking, use of cortisone drops, cardiovascular heart disease and sunlight exposure increase the risk for cataract, while use of hat and vision repair spectacles act protectively.
We conducted a case-control study to assess the association between diet and risk of cataract in Athens, Greece. Totals of 314 cases and 314 frequency-matched controls of both sexes, aged 45-85 years and attending the ophthalmology department of a major teaching hospital in Athens, Greece, were included in the study. All participants were interviewed using a semi-quantitative food-frequency questionnaire, covering the average frequency of consumption of about 120 food items. Analyses were conducted through multiple logistic regression. The analysis was carried out taking cataract as a general outcome (all types of cataract combined) and repeated by the specific type of cataract. We found significant inverse associations of cataract with dietary consumption of fish (OR = 0.69, p < 0.001), vegetables (OR = 0.47, p < 0.001), fruits (OR = 0.53, p < 0.001), and potatoes (OR = 0.76, p = 0.004), while consumption of meat was positively associated with cataract (OR = 1.46, p = 0.001). High intake of total fat (OR = 2.00, p < 0.001) and cholesterol (OR = 1.65, p < 0.001) increased the risk of cataract. There was a protective association between cataract risk and intake of carbohydrates (OR = 0.39, p < 0.001), carotene (OR = 0.56, p < 0.001), vitamins C and E (OR = 0.50, p < 0.001 and OR = 0.50, p < 0.001 respectively). We identified an association between the risk of cataract and several food groups and nutrients. Diets rich in fruits, vegetables, fish, pulses and starchy foods may protect against cataract. In addition, high intake of vitamins C and E and carotene with reduction of intake in total fat and cholesterol may be beneficial. Dietary advice along these lines may provide adequate public health guidelines for the delay of age-related cataract.
Background/Aims: To evaluate changes in macular thickness measured by optical coherence tomography (OCT) during a hemodialysis (HD) session in diabetic patients with end-stage renal disease. Methods: 72 eyes of 36 diabetic patients with and without macular edema were evaluated before and immediately after an HD session. Average and maximum macular thicknesses in the central disk (6 mm in diameter) and total macular volume were measured. Results: In the eyes with diabetic macular edema, maximum macular thickness within the central disk of 6 mm, and mainly in its peripheral parts, was significantly reduced by 31.18 ± 4.18 µm after HD (p < 0.001). Average macular thickness and total macular volume were also significantly reduced (p = 0.003 and 0.015, respectively). In diabetic eyes without edema, maximum macular thickness decreased significantly by 11.21 ± 1.98 µm after HD (p < 0.001), while average macular thickness and total macular volume decreased slightly (p = 0.034, p = 0.043). Best-corrected visual acuity failed to change. We found a significant association of macular thickness changes with osmolality reduction and the presence of macular edema. Conclusion: HD decreases macular thickness in diabetic patients with macular edema, while there exists a less-pronounced effect in diabetic eyes without edema.
Our results suggest that both topical and subconjunctival bevacizumab achieve significant reduction in the area of corneal NV. This meta-analysis provides an evidential basis for the new therapeutic concept of treating corneal NV with antiangiogenic therapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.