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T. Sherpa, M. P. Gray, B. A. Link, D. L. Stenkamp; Ongoing Proliferation and Regenerative Responses in the Zebrafish Bug Eye Mutant. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3043.
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The zebrafish mutant, bug eye, shows multiple glaucoma-related phenotypes including elevated IOP, retinal cell death with progressive blindness, and complex genetics. The wildtype fish retina responds to injury with a cell proliferative response that leads to retina regeneration and the restoration of vision. Our long term goal is to determine to what extent the bug eye mutant retina can accomplish this regenerative response.
To assess the capacity for retinal cell proliferation, bug eye fish (at 4 months, 6 months and 1 year) were immersed in 5 mM bromodeoxyuridine (BrdU) for three days, and were sacrificed 4 days later. Histological methods were then used to measure cell proliferation, ganglion cell number, and optic nerve head thickness.
The bug eye mutant shows progressive loss of retinal ganglion cells over time, and the retina in general becomes progressively disorganized. The optic nerve head diminishes in thickness but does not completely disappear. As the bug eye fish ages, retinal cell proliferation (incorporation of BrdU) continues at a high rate as compared to wildtype fish.
The bug eye mutant provides a tractable model organism for studying cell death in eyes with elevated IOP. These studies further suggest bug eye as a model for understanding the capacities for in vivo regenerative responses that take place amid genetically-mediated pathology. We are currently characterizing the specific cell types that are generated in the adult bug eye retina, with the goal of determining the point at which the native regenerative process may fail to restore vision. Our findings have broad implications for applying regenerative therapies to glaucoma patients.
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