Increased elastin expression in astrocytes of the lamina cribrosa in response to elevated intraocular pressure

PURPOSE. To determine whether abnormal elastin synthesis in the glaucomatou s optic nerve head and lamina cribrosa is due to elevated intraocular press ure (IOP) or 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 to 45 nim. Hg for 7 to 36 weeks. In 6 monkeys, un ilateral, optic nerve transection was performed, and monkeys were killed af ter 4 weeks. Optic nerve damage was assessed by stereoscopic slit-lamp biom icroscopy and fundus photography and by confocal scanning laser ophthalmosc opy. The eyes were enucleated and processed for immunohistochemistry and in situ hybridization and for electron microscopic immunogold detection of el astin. Axonal loss was evaluated in cross sections of the optic nerve stain ed with phenylenediamine. RESULTS. Compared with normal contralateral controls, the lamina cribrosa o f eyes with elevated IOP exhibited markedly increased elastin and the prese nce of elastotic: aggregates in the extracellular matrix and upregulation o f elastin mRNA in the astrocytes. In transected eyes, elastin appeared as f ine fibers in the lamina cribrosa, without elastotic aggregates, and withou t 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 demonstrates that abnormal elastin synthesis in exp erimental glaucomatous optic neuropathy in the monkey is specific to elevat ed IOP and not secondary to axonal loss. The mechanisms by which elevated I OP induces enhanced elastin synthesis in laminar astrocytes are unknown but differ from those involved in acute axonal injury such as transection, whe re inflammation and breakdown of the bloodnerve barrier occur.