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L. Wang, B. Fortune, G. Cull, J. Dong, G.A. Cioffi; Endothelin B Receptor Expression in Glial Cells after Ganglion Cell Axon Transection . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3326.
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Purpose: The glial cell endothelin system may mediate neuronal damage in the CNS. This study investigated the response of the endothelin B receptor (ETbR) in glial cells of the retina and optic nerve after surgical optic nerve transection and laser intraretinal axotomy. Methods: The optic nerve one eye in four albino rabbits was surgically transected. In one eye of one monkey, a bundle of axons ~2mm adjacent to optic disc was severed using green laser photocoagulation. One month after the optic nerve transection in rabbits and eight months after the first laser photocoagulation in the monkey, the eyes and the optic nerves were processed for paraffin sections and stained immunohistochemically with endothelin B receptor antibodies. Selectively, the stain was combined with GFAP, CA II or 5-D-4, specific glial cell markers for astrocytes, Muller cells and microglia, respectively. Results: In rabbit eyes with optic nerve transection, the retinal nerve fiber layer was thinner and had less ganglion cells compared with the normal eyes. High immunoreactivity (IR) of ETbR was observed in the nerve fiber layer and ganglion cell layer. These ETbR positive cells were co-localized with macroglial cells, but not microglia. No ETbR IR was observed in the retinas of normal eyes. At the site where the transection was made in the optic nerve in rabbits, strong ETbR IR was found largely in microglia, but not in the astrocytes, though both types of glial cells showed an increase in number and exhibited reactive morphological changes. In the anterior portion of the retrolaminar optic nerve, ETbR IR was also found in microglia and some GFAP positive cells in both normal and transected optic nerves, with higher density of ETbR IR cells in the transected optic nerves. In monkey, a regional axonal degeneration was observed in the optic nerve. Within this region, there was an increased number of astrocytes and microglia, as well as stronger ETbR IR in microglia compared to the region without axonal damage. Conclusions: The increased ETbR–IR in glial cells in both retina and optic nerve after the ganglion cell axons transection in both retina and optic nerve suggest that the Glia-Endothelin System may participate in the process of neuronal degeneration.
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