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M.H. Shomer, J.M. Kwong, J. Caprioli, L.K. Gordon; Neurogenesis in the adult rat retina after intra–ocular NMDA lesion. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):882.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: De novo neurogenesis in the adult brain occurs in non–mammalian animals and was recently observed in a rat model of cortical damage (Magavi et al., 2000 Nature). Neuro–regeneration could be an exciting approach to chronic retinal ganglion cell (RGC) death, the final common pathway for progressive optic neuropathies. The purpose of this study was to determine if neurogenesis in the adult rat retina could be observed in response to cell loss, therefore testing the hypothesis that the endogenous neural stem cells could potentially be triggered to repopulate the retina in response to injury. Methods: Adult Wistar rats were anesthetized and subject to unilateral RGC damage from an intravitreal injection of 8 nmol N–methyl–D–aspartate (NMDA). This dose of NMDA reduces the number of RGCs by approximately 40%. After 3 days, the animals received daily intraperitoneal injections of 5Bromo–2deoxyuridine (BrdU), a nucleotide analog, to label cells in S phase. After 7 days, the animals were euthanized, and the eyes collected for immunohistochemical analysis. A specific antibody against BrdU was used to identify the dividing cells. Neuronal markers, betaIII tubulin and neurofilament, were visualized using specific antibodies. Dividing cells, as evidenced by BrdU labeling, were analyzed for concomitant expression of betaIII tubulin or neurofilament, and quantified. Results: The normally dividing epithelial cells in the cornea and conjunctiva were used as internal controls for BrdU labeling. Frequent BrdU+ cells were observed in these epithelial layers in both the lesioned and control eyes as anticipated. As compared to the control eyes, the lesioned eyes exhibited a 3–3.5 fold increase in the BrdU+ cells in the ciliary body and ciliary margin and a greater than 5 fold increase in the BrdU+ cells in the retina. Rare cells in the retinas of the lesioned side, but none from the controls, were observed to be triple labeled for betaIII tubulin, neurofilmant, and were BrdU+. Conclusions: These results indicate that cell division in the adult mammalian eye is stimulated after injury. Additionally, the observation of rare cells in the lesioned retinas, triple labeled for BrdU, neurofilament, and betaIII tubulin, suggest that neurogenesis in the adult mammalian retina is a possibility. Additional work is required to define these observations.
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