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Abstract #18528 Published in IGR 3-3
Increased elastin expression in astrocytes of the lamina cribrosa in response to elevated intraocular pressure
Pena JDO; Agapova OA; Gabell BT; Levin LA; Lucarelli MJ; Kaufman PL; Hernandez MRInvestigative Ophthalmology and Visual Science 2001; 42: 2303-2314
PURPOSE: To determine whether abnormal elastin synthesis in the glaucomatous optic nerve head and lamina cribrosa is due to elevated intraocular pressure (IOP) or is secondary to axonal injury, monkeys with elevated IOP and with optic nerve transection were compared. METHODS: Unilateral, chronic elevated IOP was induced in 11 rhesus monkeys by laser scarification of the trabecular meshwork. IOP was monitored weekly and maintained within 25-15 mmHg for seven to 36 weeks. In six monkeys, unilateral, optic nerve transection was performed and the monkeys were killed after four weeks. Optic nerve damage was assessed by stereoscopic slit-lamp biomicroscopy and fundus photography, and by confocal scanning laser ophthalmoscopy. The eyes were enucleated and processed for immunohistochemistry and in situ hybridization, and for electron microscopic immunogold detection of elastin. Axonal loss was evaluated in cross-sections of the optic nerve stained with phenylenediamine. RESULTS: Compared with normal contralateral controls, the lamina cribrosa of eyes with elevated IOP exhibited markedly increased elastin and the presence of elastotic aggregates in the extracellular matrix, and upregulation of elastin mRNA in the astrocytes. In transected eyes, elastin appeared as fine fibers in the lamina cribrosa, without elastotic aggregates, and without new synthesis or abnormal deposition of elastin. At the transected site, new synthesis of elastin was present in the pia mater but not in astrocytes in the glial scar. CONCLUSIONS: This study demonstrated that abnormal elastin synthesis in experimental glaucomatous optic neuropathy in the monkey is specific to elevated IOP and is not secondary to axonal loss. The mechanisms by which elevated IOP induced enhanced elastin synthesis in laminar astrocytes are unknown, but differ from those involved in acute axonal injury such as transection, where inflammation and breakdown of the blood-nerve barrier occur.
Dr M.R. Hernandez, Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, 600 S Euclid Avenue, Box 8096, St Louis, MO 63110, USA. hernandez@vision.wustl.edu
Classification:
1.3 Pathogenesis (Part of: 1 General aspects)
