Big Data Bioinformatics and Genetics of Hereditary Retinal Disorders:
The laboratory focuses on the genetics of inherited retinal disorders using state-of-the-art techniques. For complex diseases like AMD, finding clinical biomarkers of pre-clinical disease using genetic endophenotypes will identify those patients at risk for developing disease, and allow them to participate in clinical trials or seek treatments as they become available. Stargardt Disease, a juvenile onset retinal degeneration, arises from mutations in a single gene, ABCA4. Even with cutting edge genomics, the causative mutations remain unknown for many patients. The use of patient-derived fibroblasts (skin biopsies) reprogrammed into retinal cells via iPSCs provides a transcriptome-based approach to molecular genetics of this disease.
Data from large clinical datasets are also used to investigate potential correlates of systemic disorders with retinal disorders such as AMD and central serous chorioretinopathy and to investigate the late life morbidities associated with retinopathy of prematurity (as a surrogate for clinically significant premature birth).
Biological Basis and Neural Pathway associated with Light Sensitivity:
Photoallodynia/Photophobia is a common comorbidity of many ocular and systemic conditions in which light causes or enhances pain. The neural pathways for light-associated pain involve both retinal and trigeminal systems, and differ depending on the cause of photoallodynia. Using genetic, pharmacological and surgical manipulations of these different pathways helps define retinal and corneal targets for diagnostic and therapeutic approaches in the patients.
Animal models of retinal disease and disorders:
Drawing inspiration from clinical practice, a number of animal models of retinal disease or damage are being used to determine disease etiology and/or treatment options.
Genetically altered mice are used to generate a model of VHL-related retinal hemangioblastomas by selectively excising the VHL in retinal cells, providing the opportunity to identify the cell type that gives rise to hemangioblastomas, a key step in developing drugs to target these retinal tumors.
Protecting retinal neurons from ischemic insult is critical to preserving vision after a retinal stroke. Central retinal artery occlusions are being used test therapeutic approaches to reducing retinal damage and preserving function.