Role of Resveratrol in Transmitochondrial AMD RPE Cells

Nashine, Sonali; Nesburn, Anthony B.; Kuppermann, Baruch D.; Kenney, M. Cristina

doi:10.3390/nu12010159

Cited by 17 publications

(21 citation statements)

References 32 publications

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“…Nowadays, several reports indicates that RES may have a great potential in the treatment of several ocular pathologies [15,39,40]. Indeed, the antiviral effects of RES related to viral replication inhibition, as well as protein and nuclei acid synthesis and gene expression for different viruses were reported [5][6][7][8]36].…”

Section: Discussionmentioning

confidence: 99%

Antiviral bioactivity of resveratrol against Zika virus infection in human retinal pigment epithelial cells

et al. 2021

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Resveratrol (RES) is a polyphenol with increasing interest for its inhibitory effects on a wide variety of viruses. Zika virus (ZIKV) is an arbovirus which causes a broad spectrum of ophthalmological manifestations in humans. Currently there is no certified therapy or vaccine to treat it, thus it has become a major global health threat. Retinal pigment epithelium (RPE) is highly permissive and susceptible to ZIKV. This work explored the protective effects of RES on ZIKV-infected human RPE cells. RES treatment resulted in a significant reduction of infectious viral particles in infected male ARPE-19 and female hTERT-RPE1 cells. This protection was positively influenced by the action of RES on mitochondrial dynamics. Also, docking studies predicted that RES has a high affinity for two enzymes of the rate-limiting steps of pyrimidine and purine biosynthesis and viral polymerase. This evidence suggests that RES might be a potential antiviral agent to treat ZIKV-induced ocular abnormalities.Constanza A. Russo and María F. Torti have contributed equally to this work.

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Section: Discussionmentioning

confidence: 99%

Antiviral bioactivity of resveratrol against Zika virus infection in human retinal pigment epithelial cells

et al. 2021

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“…A variety of studies have examined the roles of various treatments as therapeutic targets for AMD, including antithyroid drugs, autophagy regulation, pigment epithelium-derived factor (PEDF), and antioxidant compounds such as esculetin [ 33 – 36 ]. Our most recent studies revealed that the mitochondrial-derived peptide Humanin G and, separately, the antioxidant compound resveratrol protect AMD ARPE-19 cybrids from death [ 1 , 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…Therapy for wet AMD includes AREDS formulations and several effective anti-VEGF treatments that are FDA-approved [ 1 , 10 , 11 ]. On the other hand, while eating leafy green vegetables rich in antioxidants is widely recommended for dry AMD, there are no FDA-approved treatments for this condition [ 1 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, our group has shown that AMD cybrids show increased mtDNA fragmentation, impaired levels of expression of mt transcription/replication genes, upregulated proapoptotic genes and proteins, increased mtROS levels, and decreased cellular viability in comparison to normal cybrids [ 1 ]. Our most recent studies revealed that the mitochondrial-derived peptide Humanin G and, separately, the antioxidant compound resveratrol protect AMD ARPE-19 cybrids from death [ 1 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Age-Related Macular Degeneration (AMD) Transmitochondrial Cybrids Protected from Cellular Damage and Death by Human Retinal Progenitor Cells (hRPCs)

Azzam

Chwa

et al. 2021

Stem Cells International

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Purpose. One of the leading causes of irreversible blindness worldwide, age-related macular degeneration (AMD) is a progressive disorder leading to retinal degeneration. While several treatment options exist for the exudative form of AMD, there are currently no FDA-approved treatments for the more common nonexudative (atrophic) form. Mounting evidence suggests that mitochondrial damage and retinal pigment epithelium (RPE) cell death are linked to the pathogenesis of AMD. Human retinal progenitor cells (hRPCs) have been studied as a potential restorative therapy for degenerative conditions of the retina; however, the effects of hRPC treatment on retinal cell survival in AMD have not been elucidated. Methods. In this study, we used a cell coculture system consisting of hRPCs and AMD or age-matched normal cybrid cells to characterize the effects of hRPCs in protecting AMD cybrids from cellular and mitochondrial damage and death. Results. AMD cybrids cocultured with hRPCs showed (1) increased cell viability; (2) decreased gene expression related to apoptosis, autophagy, endoplasmic reticulum (ER) stress, and antioxidant pathways; and (3) downregulation of mitochondrial replication genes compared to AMD cybrids without hRPC treatment. Furthermore, hRPCs cocultured with AMD cybrids showed upregulation of (1) neuronal and glial markers, as well as (2) putative neuroprotective factors, responses not found when hRPCs were cocultured with age-matched normal cybrids. Conclusion. The current study provides the first evidence that therapeutic benefits may be obtainable using a progenitor cell-based approach for atrophic AMD. Our results suggest that bidirectional interactions exist between hRPCs and AMD cybrids such that hRPCs release trophic factors that protect the cybrids against the cellular and mitochondrial changes involved in AMD pathogenesis while, conversely, AMD cybrids upregulate the release of these neuroprotective factors by hRPCs while promoting hRPC differentiation. These in vitro data provide evidence that hRPCs may have therapeutic potential in atrophic AMD.

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“…Ресвератрол напрямую активирует ген SIRT1, что положительно сказывается на состоянии теломер [36]. При этом ресвератрол уже показал свою эффективность в лечении ВМД, защищая клетки ПЭС от повреждений, вызванных окислительным стрессом, предотвращая преждевременную гибель клеток сетчатки и восстанавливая некоторые зрительные функции [37,38].…”

Section: терапевтические агентыunclassified

From cellular senescence towards age-related macular degeneration: the role of telomeres

Lk¹,

Abramova²,

Turkina³

et al. 2020

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С момента своего открытия теломеры и теломераза стали предметом множества исследований, сначала как механизм клеточного старения, а затем как индикатор здоровья и заболеваний у людей. Защищая концы хромосом, теломеры играют жизненно важную роль в сохранении информации в нашем геноме. В обзоре приведены результаты ранних исследований, которые в последующем стали основанием для дальнейшего, более глубокого изучения и экспериментов, также представлены исследования, демонстрирующие взаимосвязь укорочения длины теломер с нейродегенеративными заболеваниями, в частности с возрастной макулярной дегенерацией (ВМД). Кроме того, рассмотрены механизмы клеточного старения, вызванные истощением теломер. Понимание молекулярных механизмов, вовлеченных в процесс старения, может выявить новые стратегии лечения и профилактики такого возраст-ассоциированного заболевания, как ВМД. Данная патология является основной причиной потери зрения у пожилых людей после глаукомы и катаракты. ВМД диагностируется на основании характерных патологических изменений сетчатки у лиц старше 50 лет. Распространенность «сухой» и «влажной» форм ВМД варьируется в разных этнических и расовых группах по всему миру. Среди лиц одной возрастной категории можно наблюдать разные формы, распространенность и стадии ВМД. Такое наблюдение подтверждает необходимость поиска биомаркера, способного осуществлять мониторинг за процессом старения, лежащим в основе данной патологии, а также возможных причин различий в течении и исходе заболевания. В обзоре используются литературные источники, отражающие развитие представлений о проблеме.

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Role of Resveratrol in Transmitochondrial AMD RPE Cells

Cited by 17 publications

References 32 publications

Antiviral bioactivity of resveratrol against Zika virus infection in human retinal pigment epithelial cells

Antiviral bioactivity of resveratrol against Zika virus infection in human retinal pigment epithelial cells

Age-Related Macular Degeneration (AMD) Transmitochondrial Cybrids Protected from Cellular Damage and Death by Human Retinal Progenitor Cells (hRPCs)

From cellular senescence towards age-related macular degeneration: the role of telomeres

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