Senescent changes in human vision have been well documented, but the factors responsible for these changes are only partially understood. The proposed research is intended to provide fundamental data on aging of the human visual system using methods that separate the relative contributions of optical and neural mechanisms. This research builds on a program demonstrating that age-related losses in the visual pathways have a profound effect on early stage processing but are compensated to a surprising degree to maintain constancy of perception. The overarching theme of the proposed research is to understand temporal dynamics of adaptation, compensation and neuroplasticity at several time scales and levels of processing.
Aim 1 compares normal aging and early-stage age-related macular degeneration. Temporal dynamics and retinal adaptation mechanisms will be studied under scotopic and photopic conditions using the full-field and multifocal ERG. Response interactions will be analyzed to understand functional sites of aging and adaptation in the outer retina. These functional data will be correlated with sequenced opsin genes and complement factor H alleles, and with ultra-high resolution images to study photoreceptor numbers and outer retinal morphology, including relations with drusen.
Aim 2 will explore temporal dynamics and gain mechanisms under conditions that are dominated by the response of magno-, parvo- or konio-cellular pathways. The hypothesis to be tested is that the OFF subdivisions of these pathways are affected more in senescence than are the ON subdivisions. This will be evaluated by measuring a psychophysical impulse response function and by a psychophysical probe to quantify age-related changes in gain control mechanisms of magno- and parvo-cellular pathways.
Aim 3 is concerned with putative cortical compensation mechanisms. While most methods define the adaptation midpoint, the first experiment for this aim is concerned with how adaptation adjusts the range or variance of color signals along cardinal and higher-order color axes. A second study will measure adaptation to higher- order ocular aberrations using a custom adaptive optics phoropter. Finally, patients with diabetic retinopathy will be tested following retinal photocoagulation therapy to determine whether some losses in vision are compensated by expansion of areas subserving spatial summation, similarly to enlargements of spatial summation areas associated with age-related losses in photoreceptors and ganglion cells. These experiments are guided by current hypotheses about the manner in which visual performance may be affected by normal senescence and by age-related macular degeneration and diabetic retinopathy. In addition to providing basic data on the aging visual system, the experiments will provide probes for models of how the visual system adapts and compensates for degradations in the optical and neural images that occur with senescence and disease.

Public Health Relevance

The purpose of this research is to understand the optical and neural foundations of age-related changes in the human visual system. Behavioral and electrophysiological methods are used to probe sites of adaptation and neuroplasticity in the retina and higher-level visual pathways.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG004058-30
Application #
8644764
Study Section
Special Emphasis Panel (ZRG1-IFCN-H (02))
Program Officer
Chen, Wen G
Project Start
1983-09-29
Project End
2016-02-29
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
30
Fiscal Year
2014
Total Cost
$328,150
Indirect Cost
$114,372
Name
University of California Davis
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Panorgias, Athanasios; Tillman, Megan; Sutter, Erich E et al. (2017) Senescent Changes and Topography of the Dark-Adapted Multifocal Electroretinogram. Invest Ophthalmol Vis Sci 58:1323-1329
Marcos, Susana; Werner, John S; Burns, Stephen A et al. (2017) Vision science and adaptive optics, the state of the field. Vision Res 132:3-33
Shinomori, Keizo; Panorgias, Athanasios; Werner, John S (2016) Discrimination thresholds of normal and anomalous trichromats: Model of senescent changes in ocular media density on the Cambridge Colour Test. J Opt Soc Am A Opt Image Sci Vis 33:A65-76
Werner, John S (2016) The Verriest Lecture: Short-wave-sensitive cone pathways across the life span. J Opt Soc Am A Opt Image Sci Vis 33:A104-22
Tillman, Megan A; Panorgias, Athanasios; Werner, John S (2016) Age-related change in fast adaptation mechanisms measured with the scotopic full-field ERG. Doc Ophthalmol 132:201-12
Tregillus, Katherine E M; Werner, John S; Webster, Michael A (2016) Adjusting to a sudden “aging” of the lens. J Opt Soc Am A Opt Image Sci Vis 33:A129-36
Jonnal, Ravi S; Kocaoglu, Omer P; Zawadzki, Robert J et al. (2015) Author Response: Outer Retinal Bands. Invest Ophthalmol Vis Sci 56:2507-10
Winkler, Alissa D; Spillmann, Lothar; Werner, John S et al. (2015) Asymmetries in blue-yellow color perception and in the color of 'the dress'. Curr Biol 25:R547-8
Panorgias, Athanasios; Zawadzki, Robert J; Capps, Arlie G et al. (2013) Multimodal assessment of microscopic morphology and retinal function in patients with geographic atrophy. Invest Ophthalmol Vis Sci 54:4372-84
Parkosadze, Khatuna; Kalmakhelidze, Teona; Tolmacheva, Marina et al. (2013) Persistent biases in subjective image focus following cataract surgery. Vision Res 89:10-7

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