Houston Daily

A research team at the University of Houston has received a grant exceeding $3.6 million from the National Eye Institute to study the PRPH2 gene, which is vital for normal vision but can cause retinal diseases and blindness when mutated.

The PRPH2 gene provides instructions for making a protein that shapes the outer segment of photoreceptor cells in the retina. These cells are responsible for converting light into electrical signals, which are then interpreted by the brain as images. Mutations in this gene, of which there are more than 300 known variants, can lead to a range of retinal diseases such as retinitis pigmentosa, pattern dystrophy, cone-rod dystrophy, and various forms of macular degeneration.

Despite its importance, scientists do not fully understand how defects in PRPH2 result in these eye conditions.

“We 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,” said Muna Naash, John S. Dunn Endowed Professor of Biomedical Engineering at UH.

Naash’s research partner is Muayyad Al-Ubaidi, John & Rebecca Moores Professor of Biomedical Engineering. “We will also examine how these cells are built and organized, and how proteins are transported to their outer segments,” said Naash.

With many mutations linked to eye diseases, PRPH2 has become an important target for developing gene therapy approaches.

“Despite considerable scientific advancement, there are still no clinically viable therapeutic options for PRPH2 retinal diseases,” Al-Ubaidi said. “Gaining a thorough grasp of the mechanisms associated with PRPH2 diseases is crucial for designing effective therapies.”

To fill these gaps in knowledge, Naash and Al-Ubaidi have created experimental models and therapeutic platforms to evaluate disease mechanisms and test potential treatments for disorders related to PRPH2.

“Our focus is to further explore the biochemical properties of PRPH2 and its key binding partner, retinal OS membrane protein 1,” said Naash. “This 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.”

The researchers believe that addressing these previously poorly understood disease mechanisms could lead to better therapeutic strategies for those affected by genetic retinal disorders.