Full field light stimuli will be used to examine how visual adaptation, mainly a photoreceptor phenomenon, affects the human cone and rod electroretinogram (ERG) of normal subjects and those affected by genetically and clinically defined forms of retinal degeneration. The research builds on a new technique in which the adapting light is the independent variable and the test light used to elicit the ERG is kept constant. Light adaptation reduces the amplitude and implicit times of the cone ERG, thereby providing information about the physiology of the cone photoreceptor. These reductions in amplitude and implicit time are independent of the amplitude of the response and therefore of the total number of receptors responding. The proposed new research will extend our studies which have shown that the cone ERGs of all RP subjects studied so far do not adapt normally. Most but not all of the defect can be explained by a reduction of cone pigment density. There are major differences between different forms of RP. In particular patients with Leber's Amaurosis are virtually incapable of any form of light adaptation, a most remarkable phenomenon. During the course of this grant the range over which we can examine light and dark adaptation will be expanded by increasing the full field adapting light by a factor of four, from 15,000 to 60,000 photopic Trolands, thus making it possible to study more completely photochemical as well as neural factors involved in adaptation. The technique will be used to examine light and dark adaptation of the middle (M) and long (L) wavelength sensitive cone ERG, the short (S) wavelength cone ERG and the rod ERG. In addition full field action spectra based on constant response criteria will be used to identify these responses. These methods will be used on a larger sample of normal subjects and patients with different forms of retinal degenerations including some we have not yet examined. These results are relevant to the diagnosis and understanding of human genetic disease of the photoreceptors and/or retinal epithelium.
