title: Effect of elevated intraocular pressure on endothelin-1 in a rat model of glaucoma.
abstract: The role of endothelin-1 (ET-1) a potent vasoactive peptide, in glaucoma pathogenesis is receiving increasing attention, particularly in astroglial activation in optic nerve damage. Our laboratory has also shown that ET-1 treatment causes proliferation of cultured human optic nerve head astrocytes to possibly initiate astrogliosis. ET-1 is distributed in retina, optic nerve, and ciliary epithelium, however the effects of elevated intraocular pressure (IOP) (as seen in glaucoma) on ET-1 and ET(B) receptors are not clearly understood. In the present study, the levels of immunoreactive ET-1 (ir-ET-1) in aqueous humour (AH) and optic nerve head (ONH) were determined in the Morrison elevated IOP model of glaucoma. Additionally in the ONH of these rats, immunohistochemical analyses of ET(B) receptors and glial fibrillary acidic protein (GFAP; a marker for astroglial cells and for astrogliosis) were performed. There was 2- to 2.5-fold increase in AH ir-ET-1 levels for rats subjected to elevated IOP, compared to their respective controls. In the Morrison rat model of glaucoma, elevated IOP increased optic nerve ir-ET-1 with concomitant increases in ir-ET(B) and ir-GFAP labelling (possibly indicative of astrogliosis and hypertrophy). As seen in brain astrocytes subjected to neurotrauma, the present findings are suggestive of ET-1's role in astroglial activation, particularly in response to elevated IOP in glaucoma.
authors.affiliation: Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107, USA. gprasann@hsc.unt.edu
authors.forename: Ganesh
authors.initials: G
authors.lastname: Prasanna
authors.forename: Christina
authors.initials: C
authors.lastname: Hulet
authors.forename: Devashish
authors.initials: D
authors.lastname: Desai
authors.forename: Raghu R
authors.initials: RR
authors.lastname: Krishnamoorthy
authors.forename: Santosh
authors.initials: S
authors.lastname: Narayan
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Brun
authors.forename: Angela M
authors.initials: AM
authors.lastname: Suburo
authors.forename: Thomas
authors.initials: T
authors.lastname: Yorio
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000378:metabolism* / Q000502:physiology; D005901:Glaucoma / Q000139:chemically induced / Q000378:metabolism*; D007429:Intraocular Pressure / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D012462:Saline Solution, Hypertonic / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D012462:Saline Solution, Hypertonic