Microvesicle Release of Mislocalized Rhodopsin from the Photoreceptor Inner Segment

The protein called rhodopsin absorbs light in our rod and cone photoreceptor cells. Rhodopsin is highly enriched in the part of the cell performing this function but could be mislocalized in some forms of human retinal degenerative diseases. This research, presented at the 2023 International Symposium on Retinal Degeneration, presented by Tylor Lewis, PhD demonstrates the existence of an active mechanism whereby such mislocalized rhodopsin is expelled from the cell in small vesicles, presumably to protect the cell from adverse effects of protein mislocalization. We also found that reducing the levels of rhodopsin in sick photoreceptor cells significantly delays their degeneration caused by mislocalized rhodopsin, suggesting that controlling rhodopsin levels may be an effective therapy for some cases of retinal degenerative disease. 

Our work suggests that reducing rhodopsin expression could serve as a gene-therapy strategy to ameliorate photoreceptor loss in a range of inherited retinal degenerative diseases. Furthermore, it sets up a future research direction exploring whether modulating the vesicle release process in a desired direction could serve as a potential therapeutic approach for treating some cases of vision loss.

Tylor Lewis, PHD is a postdoctoral fellow in the lab of Vadim Arshavsky, PhD, Helena Rubinstein Foundation Distinguished Professor of Ophthalmology and Scientific Director for Ophthalmology.