Inherited retinal dystrophies (IRDs) are a broad group of neurodegenerative disorders associated with reduced or deteriorating visual system. In the retina, cells are under constant oxidative stress due to several environmental factors, particularly light exposure and physiological stress, making photoreceptors and retinal ganglion cells more susceptible to cell death. Inherited mutations in relevant genes that contribute to citoprotective mechanisms such as autophagy and cell resilience to light and oxidative stress tip the scales towards neuronal apoptosis.
Our group has long been interested in identifying genes responsible for retinal dystrophy, and was the first to identify CERKL, a retinitis pigmentosa and cone-rod dystrophy causative gene. The precise physiological function of CERKL is yet to be determined but all evidences point to a key gene on lipid metabolism and mRNA protection required to maintain photoreceptor and ganglion cells homeostasis. Last September, during the RD2018 meeting in Ireland, we presented our results on the role of CERKL to protect retinal cells from oxidative stress. Our research group has generated in vitro and in vivo models by using primary cultures of mouse retinal cells, as well as retinas from mutant mice created by CRISPR-Cas9 gene editing and for the first time, human- retinal cups derived from patient’s induced pluripotent stem cells (iPSCs).
By deepening our understanding on CERKL protective role in the retina, we aim not only to accrue knowledge on the physiology of the retina in health and disease, but also to pave the way for new therapies, which aim to protect retinal cells that are more vulnerable to stress due to gene mutations by promoting cell resilience and survival.