The objectives of the proposed research are to 1) more narrowly define homogeneous subgroups of retinitis pigmentosa (RP), 2) characterize the natural course of the spread of retinal degeneration in RP, and 3) describe the pathophysiology of visual function loss in RP. We propose to perform over a period of five years annual follow-up measures of 1) visual fields, 2) electroretinogram intensity-response and flicker-phase functions, 3) static two-color perimetric absolute thresholds, 4) rhodopsin density, photosensitivity, and regeneration kinetics by densitometry, and 5) focal psychophysical thresholds in relation to fundus features using our stimulator fundus camera. These results will enable us to characterize the nature of the spread of retinal degeneration. To characterize the pathophysiology of visual function loss we propose perimetric measures of flash-on-flash increment thresholds on different steady backgrounds and at different times in relation to the onset and offset of the background. These results will yield information about photoreceptor neural adaptation mechanisms in RP. Subgroupings of RP will be more narrowly defined based on cross-comparisons of natural history and visual function data. We will extend our segregation analyses to test various genetic hypotheses for the different functional subgroups of RP.
