Thousands of patients including many young children become blind from retinitis pigmentosa and allied diseases. No treatments are known for practically all types. Research is proposed to gain more understanding of the pathogenesis of these diseases through assessing the diurnal rhythm in the rod electroretinogram (ERG) as a measure of rod outer segment renewal in patients with different stages and genetic types of these diseases and in normal subjects. In addition, rod ERGs measured at various times of the day will be used to determine whether or not an abnormal diurnal rhythm exists in the miniature French poodle with rod-cone degeneration and in the Royal College of Surgeons rat with hereditary retinal degeneration at various stages of rod degeneration. Results will be compared with observations on the diurnal rhythm of normal French poodles and normal rats. At corresponding times in the diurnal cycle, ERGs from the normal rats and poodles will be compared with histologic observations of outer segment length and of numbers of phagosomes in the pigment epithelium. The natural history of retinal malfunction in the miniature French poodle with rod-cone degeneration will also be monitored with electrophysiological testing; waveforms obtained at different stages will be compared with responses obtained from humans with hereditary retinal diseases. Electroretinographic testing and histologic studies will be done in the isolated cat eye perfused with pharmacologic agents thought to lead to photoreceptor and/or pigment epithelial cell death in hereditary retinal degenerations; attention will be given to whether or not these agents produce abnormal ERGs similar to those seen in human hereditary retinal degenerations. Electroretinographic studies of patients with retinitis pigmentosa will also be done to determine if delays in cone b-waves implicit time under light-adapted conditions, characteristic of progressive forms of these diseases, are secondary to abnormal rod-cone interaction and/or delays in cones a-wave latency. Obligate female carriers of sex-linked choroideremia will be evaluated with the ERG to determine to what extent the ERG can be used to detect carriers of this condition.
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