Marina Gorbatyuk, PhD

University of North Texas - Visionary

Project Title: "Anti-apoptotic Gene Therapy for ADRP rat model"

 

This project is focused on the elucidation of the roles of pro-apoptotic proteins CHOP/GADD153 and caspase-7 in provoking apoptosis in autosomal dominant retinitis pigmentosa (ADRP) photoreceptors affected by mutated rhodopsin (RHO) and design anti-apoptotic gene therapy for ADRP rat model. Retinitis pigmentosa (RP) is the most common inherited form of blindness, affecting about 1 in every 4000 people in all ethnic groups worldwide. RP can be transmitted either as an autosomal dominant (ADRP), autosomal recessive (ARRP), or X-linked trait. More than 100 mutations in rhodopsin account for approximately 30% of ADRP cases with varying severity of visual impairment. Misfolded opsin causes endoplasmic reticulum (ER) stress by interfering with the trafficking of wild-type rhodopsin, accumulating in the ER and stimulating a signal transduction cascade in ADRP photoreceptors known as the Unfolded Protein Response (UPR). If unchecked, this pathway triggers photoreceptor death through activation of apoptosis. Although supplementation with vitamin A may be beneficial in some cases, currently, there is no effective pharmacological therapy for ADRP. Therefore, the major objective of this proposal is to determine whether gene therapy based on the blockage of the ER stress associated apoptosis is a viable treatment.