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J. A. Kiland, B. T. Gabelt, T. J. Bunch, E. Lütjen-Drecoll, P. L. Kaufman; The Effect of the A.G.E. Crosslink Breaker ALT-711 on Accommodation, Outflow Facility, IOP, and Anterior Segment Morphology. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1620. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the effect of the advanced glycation endproduct (AGE) cross-link breaker ALT-711 on accommodation (ACC), outflow facility (OF), intraocular pressure (IOP), and anterior segment morphology in monkeys.
Baseline IOP (Goldmann applanation), baseline refraction and ACC (Hartinger coincidence refractometer) response to i.m. pilocarpine (PILO), baseline OF (2-level constant pressure perfusion), OF and ACC response to i.v. PILO during OF measurements, were measured in 3 rhesus monkeys (ages 19-20). After 4-6 weeks recovery, monkeys received 4 intracameral (int.cam.) (43.68µg/14µl, final concentration=~1mM) and 4 intravitreal (int.vit.) (780µg/25µl, final concentration=~1mM) injections of ALT-711 to one eye over the course of 2.5-3 weeks; vehicle (Bárány’s mock aqueous humor) was given to the opposite eye. ACC response to i.m. PILO was measured 1 week and 2, 4, and 6 months after the last injection of ALT-711 or vehicle. OF and ACC responses before and after i.v. PILO were measured 2 weeks and 2, 4, and 6 months post-injections. IOP was measured prior to all injections, ACC, and OF measurements.
There was no significant difference in pre-PILO refraction or ACC response to i.m. or i.v. PILO at any time-point when comparing ALT-treated to control eyes. Post ALT-711 baseline OF prior to i.v. PILO was and OF response to i.v. PILO was not significantly higher in ALT-treated eyes when compared to control eyes or to their respective baseline (pre-ALT-711 injections) responses to PILO at any time-point. IOP was not significantly different in treated vs. control eyes at any time-point following injections of ALT-711 or vehicle. The ALT-711 treated eyes in all 3 monkeys showed focal plaque formation in the juxtacanalicular meshwork/inner wall of Schlemms canal with aggregates clumped in some, not all, regions. Plaques were similar to those seen in POAG and in greater abundance than found in contralateral control eyes.
Intraocular injections of high concentrations of an AGE crosslink breaker ALT-711 (1mM) do not appear to affect ACC or OF responses to PILO in monkeys, and have no significant effect on IOP. However, ALT-711 appears to cause glaucomatous-like plaques in the conventional outflow pathways of non-human primates. Whether these plaques result from AGE fragments that adhere to the inner-wall elastic fibrils is not known. However, the regional distribution of plaques was insufficient to increase IOP or decrease OF in our monkeys. Studies in additional animals are forthcoming.
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