scholarly journals The role of microbiome in age-related macular degeneration: A review of the literature

2021 ◽  
Author(s):  
Athanasios Zisimopoulos ◽  
Olga Klavdianou ◽  
Panagiotis Theodossiadis ◽  
Irini Chatziralli
Keyword(s):  
Macular Degeneration ◽  
Human Microbiome ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Current Evidence ◽  
Severe Visual Loss ◽  
Age Related ◽  
New Treatment ◽  
Functional Profiles

Background: Age-related macular degeneration (AMD) is a progressive, multifactorial, degenerative disease and the leading cause of severe visual loss in the elderly population. The exact pathogenesis of AMD remains elusive, being the combination of genetic, environmental, metabolic and functional processes. Better understanding of the disease’s pathophysiology leads to new treatment targets. Human microbiome seems to be a potential therapeutic pathway for AMD, as it has been recently proven to play a role in its pathogenesis. Summary: This review shed light into the association between microbiome and AMD. Key messages: The current evidence based on the existing literature shows that there are differences in taxonomical and functional profiles in human microbiome between patients with AMD and controls, suggesting that microbiome is implicated in AMD onset and progression, being a link between AMD and nutrition/diet. Additionally, specific bacterial classes have been proposed as potential biomarkers for AMD diagnosis. Further randomized clinical studies with large sample are needed to elucidate the role of microbiome in AMD and to draw more solid conclusions.

scholarly journals The Controversial Role of TGF-β in Neovascular Age-Related Macular Degeneration Pathogenesis

2018 ◽  
Vol 19 (11) ◽  
pp. 3363 ◽  
Author(s):  
Gian Tosi ◽  
Maurizio Orlandini ◽  
Federico Galvagni
Keyword(s):  
Macular Degeneration ◽  
Visual Loss ◽  
The Elderly ◽  
Developed Countries ◽  
Age Related Macular Degeneration ◽  
Transforming Growth Factors ◽  
Severe Visual Loss ◽  
Age Related ◽  
Experimental Approaches

The multifunctional transforming growth factors-beta (TGF-βs) have been extensively studied regarding their role in the pathogenesis of neovascular age-related macular degeneration (nAMD), a major cause of severe visual loss in the elderly in developed countries. Despite this, their effect remains somewhat controversial. Indeed, both pro- and antiangiogenic activities have been suggested for TGF-β signaling in the development and progression of nAMD, and opposite therapies have been proposed targeting the inhibition or activation of the TGF-β pathway. The present article summarizes the current literature linking TGF-β and nAMD, and reviews experimental data supporting both pro- and antiangiogenic hypotheses, taking into account the limitations of the experimental approaches.

scholarly journals Novel Programmed Cell Death as Therapeutic Targets in Age-Related Macular Degeneration?

2020 ◽  
Vol 21 (19) ◽  
pp. 7279 ◽  
Author(s):  
Ming Yang ◽  
Kwok-Fai So ◽  
Wai Ching Lam ◽  
Amy Cheuk Yin Lo
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Macular Degeneration ◽  
Molecular Mechanisms ◽  
Cell Damage ◽  
Retinal Pigment ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Severe Visual Loss ◽  
Age Related

Age-related macular degeneration (AMD) is a leading cause of severe visual loss among the elderly. AMD patients are tormented by progressive central blurring/loss of vision and have limited therapeutic options to date. Drusen accumulation causing retinal pigment epithelial (RPE) cell damage is the hallmark of AMD pathogenesis, in which oxidative stress and inflammation are the well-known molecular mechanisms. However, the underlying mechanisms of how RPE responds when exposed to drusen are still poorly understood. Programmed cell death (PCD) plays an important role in cellular responses to stress and the regulation of homeostasis and diseases. Apart from the classical apoptosis, recent studies also discovered novel PCD pathways such as pyroptosis, necroptosis, and ferroptosis, which may contribute to RPE cell death in AMD. This evidence may yield new treatment targets for AMD. In this review, we summarized and analyzed recent advances on the association between novel PCD and AMD, proposing PCD’s role as a therapeutic new target for future AMD treatment.

Age-related Macular Degeneration – Review and Current Concepts

2011 ◽  
Vol 05 (01) ◽  
pp. 84
Author(s):  
Rajeev K Seth ◽  
Eric J Sigler ◽  
Ron A Adelman ◽  
◽  
◽  
...  
Keyword(s):  
Macular Degeneration ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Health Concern ◽  
Treatment Modalities ◽  
Close Monitoring ◽  
Age Related ◽  
Significant Public Health Concern ◽  
Significant Public Health ◽  
New Treatment

Age-related macular degeneration (ARMD) continues to be a significant public health concern, given its high prevalence and potential blinding prognosis in the elderly. Several risk factors have been identified in the development of ARMD, including age, race and family history. The pathogenesis of ARMD continues to be elucidated and recent research has focused on genetic factors. ARMD presents in either the atrophic or exudative form. Treatment for atrophic disease consists of antioxidants and zinc and close monitoring. Treatment for exudative disease is aimed at targeting choroidal neovascularisation. The development of anti-vascular endothelial growth factor (anti-VEGF) agents has revolutionised the treatment of exudative ARMD, providing a more favourable prognosis for previously blinding disease. A considerable amount of research is being carried out on new treatment modalities for both the atrophic and exudative forms of the disease.

scholarly journals Altered photoreceptor metabolism in mouse causes late stage age-related macular degeneration-like pathologies

2020 ◽  
Vol 117 (23) ◽  
pp. 13094-13104 ◽  
Author(s):  
Shun-Yun Cheng ◽  
Joris Cipi ◽  
Shan Ma ◽  
Brian P. Hafler ◽  
Rahul N. Kanadia ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Mammalian Target Of Rapamycin ◽  
The Elderly ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Photoreceptor Outer Segment ◽  
Metabolic Adaptations ◽  
Age Related ◽  
Disease Stages

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. While the histopathology of the different disease stages is well characterized, the cause underlying the progression, from the early drusen stage to the advanced macular degeneration stage that leads to blindness, remains unknown. Here, we show that photoreceptors (PRs) of diseased individuals display increased expression of two key glycolytic genes, suggestive of a glucose shortage during disease. Mimicking aspects of this metabolic profile in PRs of wild-type mice by activation of the mammalian target of rapamycin complex 1 (mTORC1) caused early drusen-like pathologies, as well as advanced AMD-like pathologies. Mice with activated mTORC1 in PRs also displayed other early disease features, such as a delay in photoreceptor outer segment (POS) clearance and accumulation of lipofuscin in the retinal-pigmented epithelium (RPE) and of lipoproteins at the Bruch’s membrane (BrM), as well as changes in complement accumulation. Interestingly, formation of drusen-like deposits was dependent on activation of mTORC1 in cones. Both major types of advanced AMD pathologies, including geographic atrophy (GA) and neovascular pathologies, were also seen. Finally, activated mTORC1 in PRs resulted in a threefold reduction in di-docosahexaenoic acid (DHA)–containing phospholipid species. Feeding mice a DHA-enriched diet alleviated most pathologies. The data recapitulate many aspects of the human disease, suggesting that metabolic adaptations in photoreceptors could contribute to disease progression in AMD. Identifying the changes downstream of mTORC1 that lead to advanced pathologies in mouse might present new opportunities to study the role of PRs in AMD pathogenesis.

Age-related Macular Degeneration—Review and Current Concepts

2011 ◽  
Vol 04 (01) ◽  
pp. 96 ◽  
Author(s):  
Rajeev K Seth ◽  
Eric J Sigler ◽  
Ron A Adelman ◽  
◽  
◽  
...  
Keyword(s):  
Macular Degeneration ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Health Concern ◽  
Treatment Modalities ◽  
Close Monitoring ◽  
Age Related ◽  
Significant Public Health Concern ◽  
Significant Public Health ◽  
New Treatment

Age-related macular degeneration (ARMD) continues to be a significant public health concern, given its high prevalence and potential blinding prognosis in the elderly. Several risk factors have been identified in the development of ARMD, including age, race, and family history. The pathogenesis of ARMD continues to be elucidated, and recent research has focused on genetic factors. ARMD presents in either the atrophic or exudative form. Treatment for atrophic disease consists of antioxidants and zinc and close monitoring. Treatment for exudative disease is aimed at targeting choroidal neovascularization. The development of anti-vascular endothelial growth factor (anti-VEGF) agents has revolutionized the treatment of exudative ARMD, providing a more favorable prognosis for previously blinding disease. Considerable amount of research is being carried out on new treatment modalities for both the atrophic and exudative forms of the disease.

scholarly journals Present and Possible Therapies for Age-Related Macular Degeneration

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Muhammad Khan ◽  
Ketan Agarwal ◽  
Mohamed Loutfi ◽  
Ahmed Kamal
Keyword(s):  
Macular Degeneration ◽  
Elderly Population ◽  
Treatment Options ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Common Cause ◽  
Age Related ◽  
Progressive Disorder ◽  
Additional Role

Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly population worldwide and is defined as a chronic, progressive disorder characterized by changes occurring within the macula reflective of the ageing process. At present, the prevalence of AMD is currently rising and is estimated to increase by a third by 2020. Although our understanding of the several components underpinning the pathogenesis of this condition has increased significantly, the treatment options for this condition remain substantially limited. In this review, we outline the existing arsenal of therapies available for AMD and discuss the additional role of further novel therapies currently under investigation for this debilitating disease.

scholarly journals Impact of neovascular age-related macular degeneration: burden of patients receiving therapies in Japan

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shigeru Honda ◽  
Yasuo Yanagi ◽  
Hideki Koizumi ◽  
Yirong Chen ◽  
Satoru Tanaka ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Productivity Loss ◽  
Work Productivity ◽  
The Elderly ◽  
Developed Countries ◽  
Age Related Macular Degeneration ◽  
Resource Utilisation ◽  
Total Work ◽  
Healthcare Resource Utilisation ◽  
Age Related

AbstractThe chronic eye disorder, neovascular age-related macular degeneration (nAMD), is a common cause of permanent vision impairment and blindness among the elderly in developed countries, including Japan. This study aimed to investigate the disease burden of nAMD patients under treatment, using data from the Japan National Health and Wellness surveys 2009–2014. Out of 147,272 respondents, 100 nAMD patients reported currently receiving treatment. Controls without nAMD were selected by 1:4 propensity score matching. Healthcare Resource Utilisation (HRU), Health-Related Quality of Life (HRQoL), and work productivity loss were compared between the groups. Regarding HRU, nAMD patients had significantly increased number of visits to any healthcare provider (HCP) (13.8 vs. 8.2), ophthalmologist (5.6 vs. 0.8), and other HCP (9.5 vs. 7.1) compared to controls after adjusting for confounding factors. Additionally, nAMD patients had reduced HRQoL and work productivity, i.e., reduced physical component summary (PCS) score (46.3 vs. 47.9), increased absenteeism (18.14% vs. 0.24%), presenteeism (23.89% vs. 12.44%), and total work productivity impairment (33.57% vs. 16.24%). The increased number of ophthalmologist visits were associated with decreased PCS score, increased presenteeism and total work productivity impairment. The current study highlighted substantial burden for nAMD patients, requiring further attention for future healthcare planning and treatment development.

scholarly journals Complement C5 is not critical for the formation of sub-RPE deposits in Efemp1 mutant mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Donita L. Garland ◽  
Eric A. Pierce ◽  
Rosario Fernandez-Godino
Keyword(s):  
Macular Degeneration ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Deposit Formation ◽  
Genetic Ablation ◽  
Age Related ◽  
Complement Dysregulation

AbstractThe complement system plays a role in the formation of sub-retinal pigment epithelial (RPE) deposits in early stages of age-related macular degeneration (AMD). But the specific mechanisms that connect complement activation and deposit formation in AMD patients are unknown, which limits the development of efficient therapies to reduce or stop disease progression. We have previously demonstrated that C3 blockage prevents the formation of sub-RPE deposits in a mouse model of EFEMP1-associated macular degeneration. In this study, we have used double mutant Efemp1R345W/R345W:C5-/- mice to investigate the role of C5 in the formation of sub-RPE deposits in vivo and in vitro. The data revealed that the genetic ablation of C5 does not eliminate the formation of sub-RPE deposits. Contrarily, the absence of C5 in RPE cultures promotes complement dysregulation that results in increased activation of C3, which likely contributes to deposit formation even in the absence of EFEMP1-R345W mutant protein. The results also suggest that genetic ablation of C5 alters the extracellular matrix turnover through an effect on matrix metalloproteinases in RPE cell cultures. These results confirm that C3 rather than C5 could be an effective therapeutic target to treat early AMD.

scholarly journals Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels

2021 ◽  
Vol 22 (3) ◽  
pp. 1296
Author(s):  
Yue Ruan ◽  
Subao Jiang ◽  
Adrian Gericke
Keyword(s):  
Oxidative Stress ◽  
Macular Degeneration ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Therapeutic Strategies ◽  
Vision Impairment ◽  
Age Related Macular Degeneration ◽  
Oxygen Species ◽  
Age Related

Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.

scholarly journals Neovascular Macular Degeneration: A Review of Etiology, Risk Factors, and Recent Advances in Research and Therapy

2021 ◽  
Vol 22 (3) ◽  
pp. 1170
Author(s):  
Arunbalaji Pugazhendhi ◽  
Margaret Hubbell ◽  
Pooja Jairam ◽  
Balamurali Ambati
Keyword(s):  
Risk Factors ◽  
Macular Degeneration ◽  
Kinase Inhibitors ◽  
Rho Kinase ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Gene Therapies ◽  
Rho Kinase Inhibitors ◽  
Age Related ◽  
Endothelial Growth Factor

Neovascular age-related macular degeneration (exudative or wet AMD) is a prevalent, progressive retinal degenerative macular disease that is characterized by neovascularization of the choroid, mainly affecting the elderly population causing gradual vision impairment. Risk factors such as age, race, genetics, iris color, smoking, drinking, BMI, and diet all play a part in nvAMD’s progression, with anti-vascular endothelial growth factor (anti-VEGF) therapy being the mainstay of treatment. Current therapeutic advancements slow the progression of the disease but do not cure or reverse its course. Newer therapies such as gene therapies, Rho-kinase inhibitors, and levodopa offer potential new targets for treatment.

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