Our group studies disease mechanisms in inherited retinal degenerations (IRDs), and evaluates efficacy and safety of potential treatments. IRDs result in vision loss due to mutations in more than 200 different genes and include diagnoses such as Retinitis Pigmentosa, Stargardt Disease, Leber Congenital Amaurosis, and others. There are multitudes of different pathological mechanisms resulting from different mutations. Our group uses non-invasive tests to link changes in retinal structure and function to underlying molecular pathology. We also develop and evaluate novel outcome measures for use in clinical trials.
July 28, 2020: Large deficit of night vision despite retained rod photoreceptors discovered in patients with class B Rhodopsin mutations - publication in Scientific Reports
A common inherited retinal disease is caused by mutations in Rhodopsin (RHO) expressed in rod photoreceptors that provide vision in dim ambient light. Approximately half of all RHO mutations result in a Class B phenotype where mutant rods are retained in some retinal regions but show severe degeneration in other regions. We determined the natural history of dysfunction and degeneration of retained rods by serially evaluating patients. Even when followed for more than 20 years, rod function and structure at some retinal locations could remain unchanged. Other locations showed loss of both vision and photoreceptors but the rate of rod vision loss was greater than the rate of photoreceptor degeneration. This unexpected divergence in rates with disease progression implied the development of a rod function deficit beyond loss of cells. The divergence of progression rates was also detectable over a short interval of two years near the health-disease transition in the superior retina. A model of structure-function relationship supported the existence of a large rod function deficit which was also most prominent near regions of health-disease transition. Our studies support the realistic therapeutic goal of improved night vision for retinal regions specifically preselected for rod function deficit in patients.
CIDECIYAN AV, Jacobson SG, Roman AJ, Sumaroka A, Wu V, Charng J, Lisi B, Swider M, Aguirre GD, Beltran WA. Rod function deficit in retained photoreceptors of patients with class B Rhodopsin mutations. Scientific Reports, 10:12552, 2020. [PubMed] [DOI] [PDF]