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James D. Lindsey, Karen X. Duong-Polk, Dustin Hammond, Panida Chindasub, Christopher Kai-shun Leung, Robert N. Weinreb; Differential Protection of Injured Retinal Ganglion Cell Dendrites by Brimonidine. Invest. Ophthalmol. Vis. Sci. 2015;56(3):1789-1804. doi: 10.1167/iovs.14-13892.
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To determine whether brimonidine protects against the retraction and loss of retinal ganglion cell (RGC) dendrites after optic nerve crush (ONC).
Fluorescent RGCs of mice expressing yellow fluorescent protein (YFP) under the control of the Thy-1 promoter (Thy1-YFP mice) were imaged in vivo and assigned to one of six groups according to dendrite structure. The mice then received brimonidine every other day starting 2 days before, or 2 or 6 days after, unilateral ONC. Control animals received vehicle every other day starting 2 days before ONC. Control animals received vehicle every other day starting 2 days before ONC. Total dendrite length, dendrite branching complexity, and the time until complete loss of dendrites were assessed weekly for 4 weeks.
Overall, brimonidine treatment significantly slowed the complete loss of RGC dendrites and significantly slowed the reduction of total dendrite length and branching complexity. Separate analysis of each RGC group showed brimonidine significantly delayed the time until complete loss of dendrites in four of the RGC groups. These delays generally were similar when treatment started either 2 days before or 2 days after ONC, but were smaller or absent when treatment started 6 days after ONC Protection against loss of total dendrite length and loss of branching complexity was observed in three of the RGC groups. In two of these RGC groups, protective effects persisted until the end of the study.
Brimonidine protects many RGC types against dendrite retraction, loss of branching complexity, and complete loss of dendrites following ONC. However, the pattern and magnitude of this protection differs substantially among different RGC types. These results indicate that requirements for RGC-protective therapies following optic nerve injury may differ among RGC types.
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