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G.A. Cioffi, L. Wang, G.A. Cull, J. Dong; Immunoreactivity of Endothelin B Receptor in Human Glaucomatous Optic Nerve . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1272.
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Purpose: In glaucoma, increased level of endothelin–1 (ET1), a potent vasomotor peptide, has been demonstrated both locally and systemically. As well, ET1 may have deleterious effects in the central nervous system, targeting neurons via pathways mediated by type B endothelin receptor (ETbR) on astrocytes. The purpose of this study was to 1) quantitatively compare the ETbR immunoreactivity in normal and glaucomatous human eyes and 2) to assess the relationship of the ETbR and the reactive glial cells in the optic nerve. Methods: Twenty–six post–mortem donor eyes from 16 glaucoma patients (82.7 ± 9.3 y) with varied duration and severity, and 10 age–matched normal (82.2 ±8.9 y) were processed for paraffin sections. Longitudinal sections across the anterior optic nerves were labeled immunohistochemically with corresponding antibodies to reveal the ETbR and glial cells. The ETbR immunoreactivity was quantified with an image analysis system and compared statistically between glaucomatous and normal optic nerves. Results: Nine out of the sixteen glaucomatous optic nerves showed different levels of ETbR immunoreactivity within the axonal bundles compared to one out of the 10 normal age–matched controls (Chi square, P=0.02). The dots–like or star–shaped ETbR immunoreactivity distributed in the fascicles of the glaucomatous optic nerve was quantitatively higher than that in the normal eyes (M–W U test: P=0.02). The ETbR was predominantly located on the astrocytic processes demonstrated by co–staining of GFAP and by detailed morphological comparison of the sites of the immunoreactivity with additional stained axons. Conclusions: The increased occurrence and statistically increased amount of ETbR in the processes of astrocytes of human glaucomatous optic nerves suggests that the glial–endothelin system is involved during the period of pathological processes of glaucomatous optic neuropathy.
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