Relating Structure to Function in Optic Neuropathies

University Of Houston, Houston TX

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Abstract

Relating Structure to Function in Optic Neuropathies Glaucoma is a progressive optic neuropathy, marked by characteristic losses of retinal ganglion cells and connective tissue remodeling, that leads to irreversible vision loss. The exact etiology and pathophysiology of the disease remains unclear. Hence, the clinical diagnosis and monitoring are dependent on measures of intraocular pressure, and an indirect assessment of retinal ganglion cells using in vivo imaging and assessment of visual function. The current clinical standards for glaucoma evaluation are effective for detecting and monitoring disease. However, current clinical testing is ineffective for determining an eye’s susceptibility to disease, and current vision testing does not completely represent functional vision. The lab's long-term goals are to refine in vivo structure and function measures to determine; 1. An eye's susceptibility to disease, 2. Its retinal ganglion cell (RGC) content, and 3. Functional changes with RGC damage/loss. This proposal has two aims, which build on our previous findings and are designed for the non-human primate, which has similar ocular anatomy and visual function as humans. Relevant to aim 1, we previously reported that the risk of retinal ganglion cell loss in experimental glaucoma was related to the viscoelastic properties of the neuroretinal rim tissue, and the extent of axial elongation following chronic pressure elevation. Myopia or nearsightedness occurs when the optics of the anterior segment focus light from a distant object in front of the retina, and axial elongation is the main contributing factor. Myopia is an independent risk factor for glaucoma. Further, like glaucoma, there is significant variability in experimental models of myopia. We hypothesize that accelerated axial elongation, with form deprivation myopia, results in connective and neural tissue remodeling, as reflected in pressure challenge experiments, both increasing the risk of ganglion cell loss. In this aim, we will also determine if eyes with greater axial elongation with form deprivation myopia or their control eyes, are eyes that develop more severe experimental glaucoma. Relevant to aim 2, we previously reported that the relationship between visual thresholds, with standard automated perimetry, and retinal ganglion cell content follows that predicted by spatial summation. Further, data from experimental glaucoma eyes were shifted up and have a larger critical area. Spatial summation can be modeled to represent the cortical pooling of spatial filters of specific spatial frequencies. Our preliminary data suggest that there are disease stage-specific losses in spatial frequency contrast, and that eyes with experimental glaucoma have either non-functional or dysfunctional cells. We hypothesize that with progressive retinal ganglion cell loss, contrast sensitivity at higher spatial frequencies is reduced before that at peak contrast, and thresholds for standard size III stimuli. Further, we will test the hypothesis that eyes that are faster progressors with experimental glaucoma will have increased neural noise, determined using the equivalent noise paradigm, indicative of dysfunctional retinal ganglion cells.