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Inherited retinal disorders and dry age-related macular degeneration are characterized by the degeneration and death of different types of photoreceptors at different rate and locations. Advancement of new therapeutic interventions such as optogenetics gene therapy and cell replacement therapies are dependent on electrophysiological measurements at cellular resolution. Here, we report the development of an optical coherence tomography (OCT) guided micro-focal multi-color laser stimulation and electroretinogram (ERG) platform for highly localized monitoring of retina function. Functional evaluation of wild type and transgenic pigs affected by retinal degeneration was carried out using OCT guided micro-focal ERG (μfERG) with selected stimulation wavelengths for S, M and L cones as well as rod photoreceptors. In wild type pigs, μfERG allowed functional recording from rods and each type of cone photoreceptor cells separately. Furthermore, functional deficits in P23H transgenic pigs consistent with their retinal degeneration phenotype were observed, including decrease in the S and M cone function and lack of rod photoreceptor function. OCT guided μfERG based monitoring of physiological function will enable characterization of animal models of retinal degenerative diseases and evaluation of therapeutic interventions at the cellular level.

OCT guided micro-focal ERG system with multiple stimulation wavelengths for characterization of ocular health