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      Crosstalk Between Microglia and Müller Glia in the Age-Related Macular Degeneration: Role and Therapeutic Value of Neuroinflammation

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          Abstract

          Age-related macular degeneration (AMD) is a progressive neurodegeneration disease that causes photoreceptor demise and vision impairments. In AMD pathogenesis, the primary death of retinal neurons always leads to the activation of resident microglia. The migration of activated microglia to the ongoing retinal lesion and their morphological transformation from branching to ameboid-like are recognized as hallmarks of AMD pathogenesis. Activated microglia send signals to Müller cells and promote them to react correspondingly to damaging stimulus. Müller cells are a type of neuroglia cells that maintain the normal function of retinal neurons, modulating innate inflammatory responses, and stabilize retinal structure. Activated Müller cells can accelerate the progression of AMD by damaging neurons and blood vessels. Therefore, the crosstalk between microglia and Müller cells plays a homeostatic role in maintaining the retinal environment, and this interaction is complicatedly modulated. In particular, the mechanism of mutual regulation between the two glia populations is complex under pathological conditions. This paper reviews recent findings on the crosstalk between microglia and Müller glia during AMD pathology process, with special emphasis on its therapeutic potentials.

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          Origin and physiological roles of inflammation.

          Ruslan Medzhitov (2008)
          Inflammation underlies a wide variety of physiological and pathological processes. Although the pathological aspects of many types of inflammation are well appreciated, their physiological functions are mostly unknown. The classic instigators of inflammation - infection and tissue injury - are at one end of a large range of adverse conditions that induce inflammation, and they trigger the recruitment of leukocytes and plasma proteins to the affected tissue site. Tissue stress or malfunction similarly induces an adaptive response, which is referred to here as para-inflammation. This response relies mainly on tissue-resident macrophages and is intermediate between the basal homeostatic state and a classic inflammatory response. Para-inflammation is probably responsible for the chronic inflammatory conditions that are associated with modern human diseases.
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            Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis.

            Wan Wong, Xinyi Su, Xiang Li … (2014)
            Numerous population-based studies of age-related macular degeneration have been reported around the world, with the results of some studies suggesting racial or ethnic differences in disease prevalence. Integrating these resources to provide summarised data to establish worldwide prevalence and to project the number of people with age-related macular degeneration from 2020 to 2040 would be a useful guide for global strategies. We did a systematic literature review to identify all population-based studies of age-related macular degeneration published before May, 2013. Only studies using retinal photographs and standardised grading classifications (the Wisconsin age-related maculopathy grading system, the international classification for age-related macular degeneration, or the Rotterdam staging system) were included. Hierarchical Bayesian approaches were used to estimate the pooled prevalence, the 95% credible intervals (CrI), and to examine the difference in prevalence by ethnicity (European, African, Hispanic, Asian) and region (Africa, Asia, Europe, Latin America and the Caribbean, North America, and Oceania). UN World Population Prospects were used to project the number of people affected in 2014 and 2040. Bayes factor was calculated as a measure of statistical evidence, with a score above three indicating substantial evidence. Analysis of 129,664 individuals (aged 30-97 years), with 12,727 cases from 39 studies, showed the pooled prevalence (mapped to an age range of 45-85 years) of early, late, and any age-related macular degeneration to be 8.01% (95% CrI 3.98-15.49), 0.37% (0.18-0.77), and 8.69% (4.26-17.40), respectively. We found a higher prevalence of early and any age-related macular degeneration in Europeans than in Asians (early: 11.2% vs 6.8%, Bayes factor 3.9; any: 12.3% vs 7.4%, Bayes factor 4.3), and early, late, and any age-related macular degeneration to be more prevalent in Europeans than in Africans (early: 11.2% vs 7.1%, Bayes factor 12.2; late: 0.5% vs 0.3%, 3.7; any: 12.3% vs 7.5%, 31.3). There was no difference in prevalence between Asians and Africans (all Bayes factors <1). Europeans had a higher prevalence of geographic atrophy subtype (1.11%, 95% CrI 0.53-2.08) than Africans (0.14%, 0.04-0.45), Asians (0.21%, 0.04-0.87), and Hispanics (0.16%, 0.05-0.46). Between geographical regions, cases of early and any age-related macular degeneration were less prevalent in Asia than in Europe and North America (early: 6.3% vs 14.3% and 12.8% [Bayes factor 2.3 and 7.6]; any: 6.9% vs 18.3% and 14.3% [3.0 and 3.8]). No significant gender effect was noted in prevalence (Bayes factor <1.0). The projected number of people with age-related macular degeneration in 2020 is 196 million (95% CrI 140-261), increasing to 288 million in 2040 (205-399). These estimates indicate the substantial global burden of age-related macular degeneration. Summarised data provide information for understanding the effect of the condition and provide data towards designing eye-care strategies and health services around the world. National Medical Research Council, Singapore. Copyright © 2014 Wong et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by .. All rights reserved.
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              Ranibizumab and bevacizumab for neovascular age-related macular degeneration.

              Daniel Martin, Maureen Maguire, Gui-shuang Ying … (2011)
              Clinical trials have established the efficacy of ranibizumab for the treatment of neovascular age-related macular degeneration (AMD). In addition, bevacizumab is used off-label to treat AMD, despite the absence of similar supporting data. In a multicenter, single-blind, noninferiority trial, we randomly assigned 1208 patients with neovascular AMD to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation. The primary outcome was the mean change in visual acuity at 1 year, with a noninferiority limit of 5 letters on the eye chart. Bevacizumab administered monthly was equivalent to ranibizumab administered monthly, with 8.0 and 8.5 letters gained, respectively. Bevacizumab administered as needed was equivalent to ranibizumab as needed, with 5.9 and 6.8 letters gained, respectively. Ranibizumab as needed was equivalent to monthly ranibizumab, although the comparison between bevacizumab as needed and monthly bevacizumab was inconclusive. The mean decrease in central retinal thickness was greater in the ranibizumab-monthly group (196 μm) than in the other groups (152 to 168 μm, P=0.03 by analysis of variance). Rates of death, myocardial infarction, and stroke were similar for patients receiving either bevacizumab or ranibizumab (P>0.20). The proportion of patients with serious systemic adverse events (primarily hospitalizations) was higher with bevacizumab than with ranibizumab (24.1% vs. 19.0%; risk ratio, 1.29; 95% confidence interval, 1.01 to 1.66), with excess events broadly distributed in disease categories not identified in previous studies as areas of concern. At 1 year, bevacizumab and ranibizumab had equivalent effects on visual acuity when administered according to the same schedule. Ranibizumab given as needed with monthly evaluation had effects on vision that were equivalent to those of ranibizumab administered monthly. Differences in rates of serious adverse events require further study. (Funded by the National Eye Institute; ClinicalTrials.gov number, NCT00593450.).
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                Author and article information

                Journal
                Journal ID (nlm-ta): Aging Dis
                Journal ID (iso-abbrev): Aging Dis
                Title: Aging and Disease
                Publisher: JKL International LLC
                ISSN (Electronic): 2152-5250
                Publication date Collection: 7 May 2024
                Publication date (Electronic): 7 May 2024
                Volume: 15
                Issue: 3
                Pages: 1132-1154
                Affiliations
                [1-ad-15-3-1132] 1Henan Eye Institute, Henan Eye Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, China.
                [2-ad-15-3-1132] 2Department of Physiology and Neurobiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China.
                Author notes
                [* ]Correspondence should be addressed to: Dr. Zong-Ming Song (Email: szmeyes@ 123456126.com ) and Dr. Ye Tao (Email: panghtoyezz@ 123456zzu.edu.cn ), Henan Eye Institute, Henan Eye Hospital, People's Hospital of Zhengzhou University, Zhengzhou, China.
                Article
                Publisher ID: ad-15-3-1132
                DOI: 10.14336/AD.2023.0823-3
                PMC ID: 11081163
                PubMed ID: 37728589
                SO-VID: 7965fac5-dfcb-45cf-ae43-c01726d2348a
                Copyright © Copyright: © 2024 Zhao et al.
                License:

                this is an open access article distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                Date received : 12 June 2023
                Date revision requested : 21 August 2023
                Date accepted : 23 August 2023
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 82101162
                Funded by: Key Research and Development and Promotion Project of Henan Province
                Award ID: 222102310061
                Funded by: Health science and Technology Innovation Outstanding Young talents training program of Henan Province
                Award ID: YXKC 2021027
                Funded by: Joint Project of Medical Science and Technology of Henan Province
                Award ID: LHGJ20200062
                Funded by: Basic Research Project of Henan Eye Institute
                Award ID: 21JCQN002
                Award ID: 21JCZD002
                This work was supported by grants from the National Natural Science Foundation of China (No.82101162), Key Research and Development and Promotion Project of Henan Province (No.222102310061), Health science and Technology Innovation Outstanding Young talents training program of Henan Province (No. YXKC 2021027), Joint Project of Medical Science and Technology of Henan Province (No. LHGJ20200062) and Basic Research Project of Henan Eye Institute (No.21JCQN002 and 21JCZD002).
                Categories
                Subject: Review

                Keywords: microglia,neurodegeneration,retina,age-related macular degeneration
                Data availability:
                Keywords: microglia, neurodegeneration, retina, age-related macular degeneration

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