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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
3R01EY008301-18S1
Application #
7883743
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Neuhold, Lisa
Project Start
1990-04-01
Project End
2011-08-31
Budget Start
2009-08-01
Budget End
2011-07-31
Support Year
18
Fiscal Year
2009
Total Cost
$218,430
Indirect Cost
Name
University of Illinois at Chicago
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
McAnany, J Jason; Alexander, Kenneth R; Kumar, Nalin M et al. (2013) Electroretinographic findings in a patient with congenital stationary night blindness due to a novel NYX mutation. Ophthalmic Genet 34:167-73
Gowrisankaran, Sowjanya; Genead, Mohamed A; Anastasakis, Anastasios et al. (2013) Characteristics of late negative ERG responses elicited by sawtooth flicker. Doc Ophthalmol 126:9-19
McAnany, J Jason; Alexander, Kenneth R; Genead, Mohamed A et al. (2013) Equivalent intrinsic noise, sampling efficiency, and contrast sensitivity in patients with retinitis pigmentosa. Invest Ophthalmol Vis Sci 54:3857-62
Gowrisankaran, Sowjanya; McAnany, J Jason; Alexander, Kenneth R (2013) Poststimulus response characteristics of the human cone flicker electroretinogram. Vis Neurosci 30:147-52
Gowrisankaran, Sowjanya; Alexander, Kenneth R (2012) Stimulus chromatic properties affect period doubling in the human cone flicker ERG. Doc Ophthalmol 125:21-9
Dhingra, Anuradha; Fina, Marie E; Neinstein, Adam et al. (2011) Autoantibodies in melanoma-associated retinopathy target TRPM1 cation channels of retinal ON bipolar cells. J Neurosci 31:3962-7
McAnany, J Jason; Alexander, Kenneth R; Lim, Jennifer I et al. (2011) Object frequency characteristics of visual acuity. Invest Ophthalmol Vis Sci 52:9534-8
McAnany, J Jason; Shahidi, Mahnaz; Applegate, Raymond A et al. (2011) Contributions of optical and non-optical blur to variation in visual acuity. Optom Vis Sci 88:716-23
Gowrisankaran, Sowjanya; Anastasakis, Anastasios; Fishman, Gerald A et al. (2011) Structural and functional measures of inner retinal integrity following visual acuity improvement in a patient with hereditary motor and sensory neuropathy type VI. Ophthalmic Genet 32:188-92
Alexander, Kenneth R; McAnany, J Jason (2010) Determinants of contrast sensitivity for the tumbling E and Landolt C. Optom Vis Sci 87:28-36

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