Thousands of patients including many young children become blind from retinitis pigmentosa and allied retinal degenerations each year. No treatments are known for practically all forms. The primary objective of this research is to help understand the pathogenesis of these diseases through electrophysiologic studies and other measures of retinal function and to seek rational bases for treatment. Rhodopsin gene mutations have recently been discovered in the leukocyte DNA of about 30% of families with dominant forms of retinitis pigmentosa; these mutations segregate perfectly with the disease and are thought to be the cause of these forms. Since these mutations provide a new basis for classifying patients, research will now focus on these patients with known gene defects. The rates of degenerations among patients with different mutations will be evaluated with respect to visual acuity, visual field and computer averaged full-field electroretinograms (ERGs). Dark-adapted two-color static perimetry will be performed to assess relative loss of rod and cone function in different retinal areas and to see if rod psychophysical threshold elevations can be related to the amount of remaining rhodopsin as measured by fundus reflectometry. Macular cone dark-adaptation will also be monitored for each mutation asa an additional measure of the course of the disease. Since considerable variability in clinical severity of disease has been observed in patients with the same mutation at a given age, dietary and medical questionnaires will be administered in search of non-hereditable risk factors that may be associated with a more or less severe course of retinal degeneration among patients with a given mutation. With respect to the health relatedness of this project, definition of rates of progression should provide a basis for more accurately estimating long-term visual prognoses than is currently possible for patients with rhodopsin gene mutations. Study of various parameters of retinal function with specialized testing procedures should help to clarify pathogenesis of this disease. Risk factor analyses of patients with the same mutation may reveal non-hereditable factors (e.g., dietary factors) associated with a more or less severe rate of degeneration, with possible implications for therapy.
