Metformin and rapamycin protect cells from vital dye–induced damage in retinal pigment epithelial cells and in vivo

Shu, Chih‐Wen; Tsen, Chui-Lien; Li, Meng-Syuan; Bee, Youn-Shen; Lin, Shi-Han; Sheu, Shwu‐Jiuan

doi:10.1007/s00417-019-04548-z

Cited by 4 publications

(4 citation statements)

References 16 publications

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“…Ageing and oxidative stress are not only known for causing increased intracellular damage but are also thought to be related to impaired autophagy [59]. Metformin is able to induce autophagy and reduce apoptosis of retinal cells caused by vital dyes, indocyanine green (ICG) and brilliant blue G (BBG), in studies on human RPE cell lines (ARPE-19) and rat models [60]. This suggests the possible role of metformin in improving autophagy processes in AMD.…”

Section: Discussionmentioning

confidence: 99%

Metformin, A Potential Role in Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

et al. 2021

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Background Currently, no generally approved medical treatment can delay the onset of age-related macular degeneration (AMD) or slow the progression of degenerative changes. Repurposing drugs with beneficial effects on AMD pathophysiology offers a route to new treatments which is faster, cost-effective, and safer for patients. Recent studies indicate a potential role for metformin in delaying AMD development and progression. In this context, we conducted a systematic review and meta-analysis to look for beneficial associations between metformin and AMD. Methods We systematically searched Medline and Embase (via Ovid), Web of Science, and ClinicalTrials.gov databases for clinical studies in humans that examined the associations between metformin treatment and AMD published from inception to February 2021. We calculated pooled odds ratio (OR) with 95% confidence interval (CI) considering a random effect model in the meta-analysis. Results Five retrospective studies met the inclusion criteria. There are no prospective studies that have reported the effect of metformin in AMD. The meta-analysis showed that people taking metformin were less likely to have AMD although statistical significance was not met (pooled adjusted OR = 0.80, 95% CI 0.54–1.05, I 2 = 98.8%). Subgroup analysis of the association between metformin and early and late AMD could not be performed since the data was not available from the included studies. Conclusions Analysis of retrospective data suggests a signal that metformin may be associated with decreased risk of any AMD. It should be interpreted with caution because of the failure to meet statistical significance, the small number of studies, and the limitation of routine record data. However prospective studies are warranted in generalizable populations without diabetes, of varied ethnicities, and AMD stages. Clinical trials are needed to determine if metformin has efficacy in treating early and late-stage AMD. Supplementary Information The online version contains supplementary material available at 10.1007/s40123-021-00344-3.

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Section: Discussionmentioning

confidence: 99%

Metformin, A Potential Role in Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

et al. 2021

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“…In hyperglycemia mouse model, metformin can alleviate retinal vasculature [ 23 ] and reduce retinal cell death [ 14 , 24 ]. In vital dye-induced damage of RPE and in retinitis pigmentosa mice model, metformin has been shown to provide protection [ [25] , [26] , [27] ]. In cell studies, metformin has demonstrated the ability to protect photoreceptors and RPE cells from acute injury and delay inherited retinal degeneration.…”

Section: Introductionmentioning

confidence: 99%

“…Several studies have demonstrated the underlying mechanisms for the protective action of metformin in various cell types. The protection is associated with decreased oxidative stress [ 28 , 29 ], increased mitochondrial energy production [ 30 ] and autophagy [ 26 ], as well as reduced VEGF-A expression [ 24 , 31 ]. Nevertheless, metformin may also directly suppress respiratory complex I, leading to deteriorate mitochondrial dysfunction and in turn activate AMP-activated protein kinase (AMPK) [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

Metformin inhibits methylglyoxal-induced retinal pigment epithelial cell death and retinopathy via AMPK-dependent mechanisms: Reversing mitochondrial dysfunction and upregulating glyoxalase 1

et al. 2023

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“…The same factors can induce the apoptosis of endothelial cells. MET inhibits apoptosis in retinal pigment epithelium cells [207] , hyperglycaemia-cultured endothelial cells and insulin islets [208] , and many more.…”

Section: Putative Mechanisms Underlying Met's Protective Effectsmentioning

confidence: 99%

Protection by metformin against severe Covid-19: An in-depth mechanistic analysis

Wiernsperger

Al‐Salameh

Cariou

et al. 2022

Diabetes & Metabolism

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Metformin and rapamycin protect cells from vital dye–induced damage in retinal pigment epithelial cells and in vivo

Cited by 4 publications

References 16 publications

Metformin, A Potential Role in Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

Metformin, A Potential Role in Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

Metformin inhibits methylglyoxal-induced retinal pigment epithelial cell death and retinopathy via AMPK-dependent mechanisms: Reversing mitochondrial dysfunction and upregulating glyoxalase 1

Protection by metformin against severe Covid-19: An in-depth mechanistic analysis

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