Kenneth Ross Alexander - US grants

The extrafoveal retina if the human eye contains both rod and cone photoreceptor systems. Once thought to function independently, rod and cone systems have been shown in recent years to interact under many experimental conditions. However, the role of these rod-cone interactions in human vision is not well understood. Interactions between rods and cones become of particular importance in ocular disorders such as retinitis pigmentosa and cone dystophy, in which visual losses in the peripheral field may be due only to alterations within rod or cone mechanisms, but also to abnormalities in rod-cone interactions. The research proposed in this application will investigate the properties of an unusual type of rod-cone interaction that has recently been discovered. Experiments have shown that in the dark-adapted eye, the unstimulated rods surrounding a flickering test stimulus substantially reduce the flicker sensitivity of the cone system at high temporal frequencies. The specific aims of the research are first, to measure the spatial and chromatic properties of this rod-cone flicker interaction in normal individuals; second, to determine whether the interaction is abnormal in certain types of color vision deficiencies, as suggested by preliminary studies; and third, to determine the locus of the interaction within the visual system by studying the interaction in selected patients with visual disorders in which the underlying pathological changes are known to occur at specific levels of the visual system. Flicker sensitivity will be measured using either a Maxwellian-view optical system (normal subjects) or a Tubinger perimeter (color deficient subjects amd patients with visual disorders). The long-term objective is to determine the mechanisms by which rods and cones interact in the detection of flicker in the normal human visual system. If the mechanism underlying peripheral flicker detection can be identified, then abnormalities in flicker detection, such as these that have been observed in patients with ocular disorders, will provide useful information concerning the pathological changes that accompany these disorders.

Retinitis pigmentosa (RP), one of the most frequently occurring blinding retinal dystrophies, is characterized functionally not only by nightblindness and peripheral visual field defects, but also by impaired foveal vision. The University of Illinois Research Center of the National Retinitis Pigmentosa Foundation Fighting Blindness has a cohort of approximately 900 well-categorized patients with RP who actively and frequently participate in basic and clinical research projects. Properly posed psychophysical tests on carefully selected individuals and subgroups of patients from this cohort provide a unique opportunity to assess the nature of the underlying pathophysiologic defects in retinal dystrophy, as well as to determine basic neural mechanisms for normal visual function. The results of such studies will also lead to the earlier detection of vision loss in RP, to more precise characterization of visual impairment in individual patients, to optimization of visual rehabilitation (low vision aids), and to more sensitive evaluation of potential therapeutic regimens. The goals of this research project are to test specific hypotheses concerning retinal functioning RP. Specifically, the project will determine the impact of RP on spatiotemporal mechanisms of vision and the ability of patients with particular subtypes of RP to process spatial and temporal visual information. In doing so, the research will also further clarify the extent and underlying mechanisms of foveal impairment in RP. The specific aims are: (1) to assess the contribution of irregularity in receptor sampling to foveal dysfunction in RP, (2) to evaluate the significance of contrast polarity and temporal parameters in the measurement of contrast sensitivity for letter identification, (3) to ascertain the relationship between detection of spatially localized, frequency band-limited visual stimuli and the complex task of letter identification, (4) to define the effect of light adaptation on properties of spatial mechanisms, and (5) to dissect the relative contributions of abnormalities in spatial vision and adaptation to temporal sensitivity losses in RP patients.

Retinitis pigmentosa (RP), one of the most frequently occurring blinding retinal dystrophies, is characterized functionally not only by nightblindness and peripheral visual field defects, but also by impaired foveal vision. The University of Illinois Research Center of the National Retinitis Pigmentosa Foundation Fighting Blindness has a cohort of approximately 900 well-categorized patients with RP who actively and frequently participate in basic and clinical research projects. Properly posed psychophysical tests on carefully selected individuals and subgroups of patients from this cohort provide a unique opportunity to assess the nature of the underlying pathophysiologic defects in retinal dystrophy, as well as to determine basic neural mechanisms for normal visual function. The results of such studies will also lead to the earlier detection of vision loss in RP, to more precise characterization of visual impairment in individual patients, to optimization of visual rehabilitation (low vision aids), and to more sensitive evaluation of potential therapeutic regimens. The goals of this research project are to test specific hypotheses concerning retinal functioning RP. Specifically, the project will determine the impact of RP on spatiotemporal mechanisms of vision and the ability of patients with particular subtypes of RP to process spatial and temporal visual information. In doing so, the research will also further clarify the extent and underlying mechanisms of foveal impairment in RP. The specific aims are: (1) to assess the contribution of irregularity in receptor sampling to foveal dysfunction in RP, (2) to evaluate the significance of contrast polarity and temporal parameters in the measurement of contrast sensitivity for letter identification, (3) to ascertain the relationship between detection of spatially localized, frequency band-limited visual stimuli and the complex task of letter identification, (4) to define the effect of light adaptation on properties of spatial mechanisms, and (5) to dissect the relative contributions of abnormalities in spatial vision and adaptation to temporal sensitivity losses in RP patients.

[unreadable] DESCRIPTION (provided by applicant): Spatial and temporal variations in contrast are a fundamental source of information about the visual environment. Therefore, the disruption of contrast processing due to retinal disease can potentially have a profound effect on the quality of life of persons afflicted with retinal degenerations. Because relatively little is known about the nature of contrast processing deficits in retinal diseases, the proposed studies will evaluate contrast coding through the use of innovative and sophisticated testing methods, including psychophysics, electroretinography (ERG), and the visual evoked potential (VEP), that are intended to target specific visual subsystems that can be affected differently by retinal pathology. The studies are focused on retinitis pigmentosa (RP), a group of hereditary retinal dystrophies that are the most frequent genetic cause of blindness in adults. Parallel investigations of control subjects will better define mechanisms of contrast processing in visually normal persons. The specific aims are: (1) to define the origin and relative contribution of postreceptoral processes to implicit time delays in the ERG of the cone system of patients with RP; (2) to identify the mechanisms underlying deficits in foveal contrast sensitivity in RP within the framework of magnocellular (MC) and parvocellular (PC) pathways; (3) to determine whether deficits in suprathreshold contrast discrimination in RP represent changes in response scaling or changes in effective contrast within the MC and PC pathways; and (4) to establish whether letter optotypes and grating stimuli provide equivalent measures of contrast sensitivity deficits in retinal disease. These aims will be accomplished through a series of studies that will test subjects recruited from a cohort of more than 1,200 well-categorized patients with RP, available through the University of Illinois Research Center of The Foundation Fighting Blindness. Given recent developments in understanding the molecular genetic basis for sight-threatening hereditary retinal dystrophies, and with clinical trials of therapeutic intervention being planned, the proposed studies are intended to provide a rational basis for developing new, more sensitive testing methods that will be of clinical value in monitoring the visual status of persons with eye disease and in assessing the outcome of potential treatment regimens.