University of Houston Researchers Receive $3.6M Grant to Study Vision-Critical Gene Linked to Retinal Disease

A research team at the University of Houston has been awarded over $3.6 million from the National Eye Institute (NEI) to investigate the role of the PRPH2 gene, which is essential for vision and implicated in several inherited retinal diseases. The study aims to uncover the mechanisms by which mutations in the gene lead to vision loss and to explore therapeutic strategies for treatment.

Focus on PRPH2: A Gene Essential for Photoreceptor Structure

The PRPH2 gene (peripherin 2) encodes a protein critical to the structure of the outer segments of photoreceptor cells, rods and cones, located in the retina. These cells are responsible for detecting light and initiating the visual process by converting light into electrical signals interpreted by the brain.

While PRPH2 is necessary for normal vision, more than 300 known mutations in the gene are associated with a broad spectrum of degenerative retinal diseases. These include retinitis pigmentosa, pattern dystrophy, cone-rod dystrophy, and various forms of macular degeneration. Despite its clinical relevance, the molecular mechanisms underlying PRPH2-related disease remain largely unexplored.

Objectives of the NEI-Funded Study

Led by Muna Naash, PhD, John S. Dunn Endowed Professor of Biomedical Engineering, and Muayyad Al-Ubaidi, PhD, John & Rebecca Moores Professor of Biomedical Engineering, the research will focus on how PRPH2 mutations affect rods and cones, and how this leads to retinal degeneration.

“We want to understand how defects with the PRPH2 gene lead to eye diseases,” said Dr. Naash. “Our main objective is to uncover the mechanisms underlying PRPH2-associated pathology, with a focus on its roles in rods and cones.”

Dr. Al-Ubaidi added that the team will also examine the cellular architecture of photoreceptors and how proteins are transported to their outer segments, which is essential for maintaining photoreceptor function.

Gene Therapy Potential and Unmet Needs

Although PRPH2 is increasingly viewed as a promising gene therapy target, clinically viable treatment options are not yet available. The team emphasizes that understanding the gene’s biological function is key to developing effective therapies.

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

Investigative Approach and Scientific Focus

To address these gaps, Drs. Naash and Al-Ubaidi have developed experimental models and therapeutic platforms to study the disease mechanisms associated with PRPH2 mutations. A major part of the investigation will focus on the gene’s biochemical properties and its interaction with retinal outer segment membrane protein 1 (ROM1).

By exploring how PRPH2 and ROM1 interact during the formation of rod and cone outer segment rims, the researchers hope to clarify a long-standing question in retinal biology. This could pave the way for future treatment development.

“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,” added Dr. Naash.