Contribution of membrane trafficking perturbation to retinal toxicity

Toxicological Sciences : an Official Journal of the Society of Toxicology
Su Khoh-ReiterShuyan Lu

Abstract

The retina is a highly structured tissue that is formed by layers containing 7 different cell types. The photoreceptor cell is a specialized type of neuron in the retina that is capable of absorbing and converting light into electrophysiological signals. There is a constant renewal process for photoreceptors consisting of intermittent shedding of the distal tips of the photosensitive outer segment and subsequent phagocytosis (uptake, degradation and recycling) by retinal pigmented epithelial (RPE) cells. This rebuilding process is essential for vision and the survival of photoreceptors and RPE cells. Drugs with a basic moiety have the potential to accumulate in the lysosome and impair its functions including the phagocytosis process, which could hinder clearance of outer segments and ultimately induce retinopathy. To determine the prevalence of this cellular mechanism in retinal toxicity, a collection of proprietary compounds associated with retinal toxicity were subjected to a battery of in vitro tests using the human adult retinal pigmented epithelium cell line, ARPE-19. The tests included a phagocytosis assay, and lysosomal and autophagosomal staining. The compounds that induced retinopathy clustered in the basic and lipophi...Continue Reading

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Citations

Mar 2, 2018·The Journal of Pharmacology and Experimental Therapeutics·Bryan F BurkeyJames E Vath
Mar 1, 2017·Proceedings of the National Academy of Sciences of the United States of America·Luz E Tavera-MendozaMyles Brown
Nov 7, 2019·Annals of Biomedical Engineering·Morgan BolgerErin Lavik
Mar 17, 2017·PloS One·Shuyan LuBart A Jessen

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An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.