In its third year, the PRPH2 Mutation Research Project is moving forward under the leadership of Radha Ayyagari, PhD and Shyamanga Borooah, MD, PhD with funding from the Nixon Visions Foundation led by philanthropists Janine and Brandon Nixon.
The research began in 2021 to study the PRPH2 gene linked to early macular degeneration and loss of central vision. This stem cell research aims to develop an early diagnosis and cure. The Nixon Visions Foundation is also partnering with the Foundation Fighting Blindness to build momentum and increase national and global research in this area.
PRPH2 is a gene which provides instructions for making a protein (peripherin 2) in the retina that plays a role in normal vision. The retina is the light sensitive part of the back of the eye. This protein is necessary for full function of specialized cells within the retina called photoreceptors that detect light and color. When mutations occur in this gene, damage to the retina causes vision to diminish progressively and possibly leads to vision loss.
Borooah’s research aims to translate lab findings into clinical treatments. In recent clinical studies, using advanced imaging techniques to track disease progression, they discovered that patients had significantly thinner retinas and decreased retinal volume over a year— potential markers for future clinical trials.
In basic science studies, Borooah’s team developed 'mini-retinas' from patient-derived stem cells, correcting the mutation in some cells. This model revealed that the mutation led to lower levels of the PRPH2 protein and fewer photoreceptors, providing a strong platform for testing potential treatments. They also tested a new CRISPR based gene-editing approach, which successfully corrected the mutation in over a quarter of cells.
Ayyagari’s lab team is investigating the mechanisms behind familial PRPH2 mutations and the associated phenotype-genotype relationships. They are focused on how these mutations affect different retinal cell types by using animal models with the familial mutation. Through detailed clinical and molecular analyses, they are identifying molecular changes in cells like rods, cones, and retinal pigment epithelial (RPE) cells, and the molecular events driving retinal pathology.
Her team is also collaborating globally, gathering clinical and genetic data from nearly 1,000 patients with PRPH2 mutations, helping to reveal the broad phenotypic variations of these mutations. Ayyagari’s animal models provide a platform to explore disease mechanisms, evaluate patient-specific therapies, and develop broader treatment strategies for PRPH2-related retinal diseases, ultimately uncovering the molecular basis of these disorders and guiding targeted treatments.
The Ayyagari and Borooah collaborative research team’s investigations are promising by potentially slowing disease progression and preserving vision in patients with PRPH2 genes.
