Amblyopia causes visual loss in 2% of the American population, despite improved standards for detection and treatment. The broad objective of this proposal is to elucidate the structural basis of amblyopia in humans. Little direct information is available about the pathological changes induced by amblyopia in human visual cortex, in part because most of the invasive experimental techniques developed for animal studies cannot be used in humans. The cytochrome oxidase (CO) method of Wong-Riley has the special advantage that it is suitable for mapping patterns of metabolic activity in human autopsy tissues. In this proposal, CO histochemistry will be applied to specimens of visual cortex obtained post-mortem from patients with a history of early visual loss.
The specific aim i s to define the timing and duration of the critical period for the plasticity of ocular dominance columns, by examining cases involving loss of visual function (or actual loss of one eye, e.g., retinoblastoma, trauma) at various ages during childhood. In addition, the patterns of CO activity in striate cortex associated with different forms of amblyopia will be tested by examining specimens from patients with well-documented histories of early unilateral cataract, strabismus, or anisometropia. CO will also be used to determine if patches are present in human newborns. To interpret the CO data from human tissues, and to further explore the structural and physiological alterations in visual cortex responsible for amblyopia, a series of correlative experiments will be performed in macaque monkeys.
The specific aims are: 1) To determine whether a gradient exists across the cortical representation of the visual field, from fovea to periphery, in the susceptibility of ocular dominance columns to shrinkage induced by visual deprivation. This will be achieved by reconstructing the entire mosaic of ocular dominance columns, labelled with CO histochemistry and proline autoradiography, in monkeys deprived at different ages by unilateral eyelid suture. 2) To determine whether ocular dominance columns in macaques are segregated at birth. This will be achieved by intraocular injection of [3H]-proline in monkeys delivered by Caesarean section 1 week before the end of normal gestation. 3) To characterize the receptive field properties and ocular dominance of cells within the foveal representation of amblyopic monkeys. This will be achieved by using quantitative electrophysiological recording techniques. 4) To determine whether visual deprivation reduces thalamic input to CO patches in V1 serving the amblyopic eye. This will be achieved by making large injections of [3H]-proline into the thalamus of visually deprived monkeys to label the patches in V1. 5) To determine whether visual deprivation causes a selective loss of projections from V1 -> V2 which serve the deprived eye. This will be achieved by injecting horseradish peroxidase into V2, and correlating the position of retrogradely labelled cells in V1 with the ocular dominance columns labelled by CO histochemistry.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY010217-01
Application #
3267413
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1993-07-01
Project End
1998-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
1
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Adams, Daniel L; Rapone, Brittany C; Economides, John R et al. (2018) Spontaneous Reattachment of the Medial Rectus After Free Tenotomy. J Pediatr Ophthalmol Strabismus 55:335-338
Economides, John R; Rapone, Brittany C; Adams, Daniel L et al. (2018) Normal Topography and Binocularity of the Superior Colliculus in Strabismus. J Neurosci 38:173-182
Horton, Jonathan C; Barkovich, A James (2017) Bilateral Optic Disc Pits With Posterior Pituitary Ectopia. J Neuroophthalmol 37:401-402
Horton, Jonathan C; Fahle, Manfred; Mulder, Theo et al. (2017) Adaptation, perceptual learning, and plasticity of brain functions. Graefes Arch Clin Exp Ophthalmol 255:435-447
Adams, Daniel L; Economides, John R; Horton, Jonathan C (2017) Incomitance and Eye Dominance in Intermittent Exotropia. Invest Ophthalmol Vis Sci 58:4049-4055
Economides, John R; Adams, Daniel L; Horton, Jonathan C (2017) Capturing the Moment of Fusion Loss in Intermittent Exotropia. Ophthalmology 124:496-504
Horton, Jonathan C (2017) Invited Commentary: Ganglion Cell Complex Measurement in Compressive Optic Neuropathy. J Neuroophthalmol 37:13-15
Economides, John R; Adams, Daniel L; Horton, Jonathan C (2016) Normal correspondence of tectal maps for saccadic eye movements in strabismus. J Neurophysiol 116:2541-2549
Adams, Daniel L; Economides, John R; Horton, Jonathan C (2016) Cortical Representation of a Myopic Peripapillary Crescent. Ophthalmology 123:1494-9
Economides, John R; Adams, Daniel L; Horton, Jonathan C (2016) Variability of Ocular Deviation in Strabismus. JAMA Ophthalmol 134:63-9

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