July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Simvastatin Protects Photoreceptors from all-trans-retinal Induced Oxidative Stress with Up-regulating Interphotoreceptors Retinoid Binding Protein
Author Affiliations & Notes
  • Ling Zhu
    Save Sight Institute, the University of Sydney, Sydney, New South Wales, Australia
  • Ting Zhang
    Save Sight Institute, the University of Sydney, Sydney, New South Wales, Australia
  • Weiyong Shen
    Save Sight Institute, the University of Sydney, Sydney, New South Wales, Australia
  • Mark C Gillies
    Save Sight Institute, the University of Sydney, Sydney, New South Wales, Australia
  • Footnotes
    Commercial Relationships   Ling Zhu, None; Ting Zhang, None; Weiyong Shen, None; Mark Gillies, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5290. doi:
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      Ling Zhu, Ting Zhang, Weiyong Shen, Mark C Gillies; Simvastatin Protects Photoreceptors from all-trans-retinal Induced Oxidative Stress with Up-regulating Interphotoreceptors Retinoid Binding Protein. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5290.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Simvastatin is an HMG-CoA (5-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitor with multiple targets and effects. It has been reported to protect neurons in brain, but its potential protective effect on photoreceptors has not been studied. Here we investigated the neuroprotective effect of simvastatin on photoreceptors exposed to stress induced by all-trans-retinal (atRAL).

Methods : Alarmar blue and Lactate Dehydrogenase (LDH) assays were used to evaluate the viability and metabolic activity of Y79 cells (Retinoblastoma cell line) exposed to atRAL-induced stress with or without simvastatin treatment. We verified our findings by measuring changes in cellular reactive oxygen species (ROS) using flow cytometry as well as changes on the mitochondrial stress markers JC-1 and HSP60. Photoreceptor-specific markers Cone-rod homeobox protein (CRX) and Interphotoreceptor retinoid binding protein (IRBP) changes were evaluated with Western blotting. Our findings were further validated using human retinal explants and a mouse model of photoreceptor degeneration.

Results : Simvastatin improved mitochondrial function and alleviated oxidative stress induced by atRAL in Y79 cells. Simvastatin treatment resulted in up-regulation photoreceptors specific markers, in particular IRBP and its upstream regulator CRX. Simvastatin increased the viability of photoreceptors and reduced cell apoptosis in human retinal explants under atRAL-induced stress, which was also in association with upregulation of IRBP and CRX protein. In vivo, simvastatin attenuated photoreceptor degeneration in association with upregulation of IRBP and CRX expression in a murine model in which photoreceptor degeneration results from knocking down IRBP.

Conclusions : Our findings suggest that simvastatin has a novel role in protecting photoreceptors from atRAL-induced stress. Simvastatin treatment resulted in upregulation of IRBP and its upstream transcription factor CRX in Y79 cells, human retinal explants and murine retinas in vivo. Further studies of the role of simvastatin as a novel treatment for photoreceptor degeneration are warranted.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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