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Abstract #25987 Published in IGR 12-2
Effect of the Age Cross-Link Breaker Alagebrium on Anterior Segment Physiology, Morphology, and Ocular Age and Rage
Kiland JA; Gabelt BT; Tezel G; Lutjen-Drecoll E; Kaufman PLTransactions of the American Ophthalmological Society 2009; 107: 146-158
Purpose: To determine the effects of the advanced glycation end product (AGE) cross-link breaker alagebrium on intraocular pressure (IOP), accommodation (ACC), outflow facility (OF), anterior segment morphology, and ocular AGE and receptors for AGE (RAGE) in older rhesus monkeys. Methods: Six rhesus monkeys (aged 19 to 20 years) received 3 or 4 intracameral and intravitreal (final concentration, 1 mM) injections of alagebrium to one eye over 2.5 to 3 weeks and vehicle to the opposite eye. ACC and OF responses to intramuscular or intravenous pilocarpine were measured at baseline and at 1 to 2 weeks and 2, 4, and 6 months postinjection. IOP was measured prior to all injections, ACC, and OF measurements. Monkeys were euthanized 3 to 6 months after the last injection, the eyes were enucleated, and anterior and posterior segments were examined by electron microscopy or immunohistochemistry. Results: No significant differences were found in ACC or IOP at any time point after alagebrium treatment. Baseline OF was higher (37.0 (plus or minus) 6.0%; P (less-than or equal to) .005) in alagebrium-treated vs control eyes at 6 months postinjection. In 3 monkeys, alagebrium-treated eyes, compared to control eyes, showed greater focal plaque formation, similar to that seen in primary open-angle glaucoma, in the juxtacanalicular meshwork/inner wall of Schlemm's canal. No changes in anterior segment AGE or RAGE were detectable. However, some areas of the retina and optic nerve head exhibited decreased AGE and increased RAGE immunostaining. Conclusions: Intraocular injection of AGE cross-link breakers is an unlikely approach for glaucoma therapy. However, it may generate a model for further study of glaucomatous-like plaque formation. Immunohistochemical changes in the posterior segment in response to alagebrium warrant further functional studies.
J. A. Kiland. Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, United States.
Classification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
5.2 Primates (Part of: 5 Experimental glaucoma; animal models)