The ability to perceive variations in contrast within the visual environment is often compromised in individuals who are undergoing retinal degeneration, and this can lead to problems in carrying out tasks of daily living. However, relatively little is known about the specific ways in which contrast coding is altered in retinal diseases. To address this deficiency, four distinct projects are proposed that have as a common theme the evaluation of spatial and temporal deficits in contrast processing within the cone system of patients with retinitis pigmentosa (RP), a group of night-blinding, hereditary retinal degenerations that are the most frequent genetic cause of blindness in adults. Concurrent investigations of contrast coding in visually normal individuals will provide new insights into the underlying mechanisms of visual processing within the normal visual system. The specific aims are: (1) to resolve an apparent contradiction between deficits in luminance contrast detection and contrast discrimination within the inferred magnocellular and parvocellular pathways in patients with RP;(2) to define the object spatial frequencies that are optimal for evaluating letter contrast sensitivity and visual acuity in retinal degenerations;(3) to determine the retinal origin and generality of a phase lag of the L-cone-driven flicker electroretinogram (ERG) in RP;and (4) to characterize the properties of synchronous period doubling in the flicker ERG of visually normal individuals and patients with RP in order to clarify the nature of the underlying mechanism. These aims will be addressed by novel and innovative psychophysical and ERG techniques applied to individuals recruited from a cohort of more than 1,400 well- categorized patients with RP, available under the auspices of the University of Illinois Research Center of The Foundation Fighting Blindness, and to age-equivalent individuals with normal vision. Recent breakthroughs have increased our understanding of the molecular genetic basis for sight-threatening retinal degenerations, and potential strategies for therapeutic interventions are under investigation, but the standard clinical methods for evaluating the functional integrity of the visual system have known limitations. The studies proposed in this application are intended to provide new methods for monitoring visual dysfunction in persons with retinal degenerations, for identifying more homogeneous patient subgroups for inclusion in clinical trials, and for evaluating the outcome of potential therapeutic strategies.

R01EY008301

1990-04-01

2012-08-31