A team of endowed professors and vision researchers at the 91破解版 has been awarded over $3.6 million by the National Eye Institute to investigate a gene in the eye, crucial for normal vision, but when mutated causes retinal diseases that lead to blindness.
When working properly, the gene 鈥� called peripherin 2 鈥� provides instructions for making a protein essential for shaping the outer segment of photoreceptor cells in the retina, the light sensitive structure responsible for capturing visual information. Photoreceptor cells are crucial because they convert light into electric signals that the brain interprets as images.
But when mutated, the PRPH2 gene, with more than 300 variants, can cause a spectrum of retinal disease, ranging from retinitis pigmentosa to cone and macula-predominant disorders like pattern dystrophy, cone-rod dystrophy and several forms of macular degeneration.
With it all, the underlying mechanisms of PRPH2 are not well understood.
鈥淲e want to understand how defects with the PRPH2 gene lead to eye diseases. Our main objective is to uncover the mechanisms underlying PRPH2-associated pathology, with a focus on its roles in rods and cones, the two types of photoreceptor cells in the retina.鈥�
鈥� Muna Naash, John S. Dunn Endowed Professor of Biomedical Engineering.
Her research partner is Muayyad Al-Ubaidi, John & Rebecca Moores Professor of Biomedical Engineering. 鈥淲e will also examine how these cells are built and organized, and how proteins are transported to their outer segments,鈥� said Naash.
With so many mutations linked to eye diseases, PRPH2 has become an important target for developing gene therapy.
鈥淒espite considerable scientific advancement, there are still no clinically viable therapeutic options for PRPH2 retinal diseases,鈥� Al-Ubaidi said. 鈥淕aining a thorough grasp of the mechanisms associated with PRPH2 diseases is crucial for designing effective therapies.鈥�
To address these knowledge gaps, Naash and Al-Ubaidi developed experimental models and various therapeutic platforms that allow them to evaluate disease mechanisms and test therapeutic strategies for PRPH2 disorders.
鈥淥ur focus is to further explore the biochemical properties of PRPH2 and its key binding partner, retinal OS membrane protein 1,鈥� said Naash. 鈥淭his will aid our understanding of the precise mechanisms governing PRPH2's involvement in rod and cone outer segment rim formation, an elusive goal that has long hindered the development of effective therapies.鈥�
Addressing these previously poorly understood PRPH2-associated disease mechanisms will pave the way for future improved therapeutic strategies, said the researchers.