Abstract (IGR: 4-2) | International Glaucoma Review #

Abstract #3386 Published in IGR 4-2

Human optic nerve head astrocytes as a target for endothelin-1

Prasanna G; Krishnamoorthy R; Clark AF; Wordinger RJ; Yorio T
Investigative Ophthalmology and Visual Science 2002; 43: 2704-2713

PURPOSE: To determine whether human optic nerve head astrocytes (hONAs) are target cells for the actions of endothelin (ET)-1, a potent vasoactive peptide, by causing astrocyte proliferation, as occurs in glaucomatous optic nerve heads. ET-1 levels are elevated in glaucomatous eyes, and administration of ET-1 to the retina causes glial activation and optic nerve damage in animal models in a manner similar to that observed in glaucoma. METHODS: Well-characterized hONAs were used in this study. Cell proliferation of hONAs was assessed, after ET-1 treatment under serum-free culture conditions, with both a formazan assay and [³H]thymidine uptake. ET receptor involvement for cell proliferation was determined with BQ788 (an ET_B antagonist), BQ610 (an ET_A antagonist), PD142893 (an ET_A/B mixed antagonist), and sarafotoxin 6C (S6C; an ET_B agonist). ET-1Binduced intracellular calcium ([Ca²⁺]_i) in hONAs was measured by fura-2 imaging. RT-PCR was used to determine whether hONAs express mRNA for preproET-1, ET_A, and ET_B receptors. RESULTS: ET-1 (10 and 100 nM) caused a time-dependent proliferation of hONAs, which was completely blocked by PD142893, as detected by two different cell proliferation assays. The effects of ET-1 were blocked by BQ788 and were also mimicked by S6C, indicative of the involvement of ET_B receptor activation. ET-1Binduced elevation in [Ca²⁺]_i, and cell proliferation were both blocked completely by the ET_A antagonist BQ610, suggesting ET_A receptor involvement. The hONAs expressed mRNA for ET_A and ET_B receptors as well as preproET-1, suggesting that these cells may also be a source for ET-1 in the optic nerve head. CONCLUSIONS: ET-1 induces astroglial proliferation in cultured human optic nerve head astrocytes through ET_A/B receptor activation. This is similar to the proliferation of ET-1 in brain astrocytes. These findings suggest that ET-1, which is elevated in glaucoma, could cause proliferation of ONAs in the optic nerve head.

Dr. G. Prasanna, Department of Pharmacology and Neuroscience, Division of Cell Biology and Genetics, University of North Texas Health Science Center, Fort Worth, TX, USA

Classification:

1.3 Pathogenesis (Part of: 1 General aspects)
4 Tissue culture of ocular cells

Issue 4-2

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Abstract #3386 Published in IGR 4-2

Human optic nerve head astrocytes as a target for endothelin-1

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Issue 4-2

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