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Abstract #58773 Published in IGR 16-3
Brimonidine prevents neurodegeneration in a mouse model of normal tension glaucoma
Semba K; Namekata K; Kimura A; Harada C; Mitamura Y; Harada TCell Death and Disease 2014; 5: e1341
Glaucoma is one of the leading causes of irreversible blindness that is characterized by progressive degeneration of optic nerves and retinal ganglion cells (RGCs). In the mammalian retina, excitatory amino-acid carrier 1 (EAAC1) is expressed in neural cells, including RGCs, and the loss of EAAC1 leads to RGC degeneration without elevated intraocular pressure (IOP). Brimonidine (BMD) is an α2-adrenergic receptor agonist and it is commonly used in a form of eye drops to lower IOP in glaucoma patients. Recent studies have suggested that BMD has direct protective effects on RGCs involving IOP-independent mechanisms, but it is still controversial. In the present study, we examined the effects of BMD in EAAC1-deficient (KO) mice, an animal model of normal tension glaucoma. BMD caused a small decrease in IOP, but sequential in vivo retinal imaging and electrophysiological analysis revealed that treatment with BMD was highly effective for RGC protection in EAAC1 KO mice. BMD suppressed the phosphorylation of the N-methyl-D-aspartate receptor 2B (NR2B) subunit in RGCs in EAAC1 KO mice. Furthermore, in cultured Müller glia, BMD stimulated the production of several neurotrophic factors that enhance RGC survival. These results suggest that, in addition to lowering IOP, BMD prevents glaucomatous retinal degeneration by stimulating multiple pathways including glia-neuron interactions.
1] Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan [2] Department of Ophthalmology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Full articleClassification:
11.3.3 Apraclonidine, brimonidine (Part of: 11 Medical treatment > 11.3 Adrenergic drugs)
9.2.4 Normal pressure glaucoma (Part of: 9 Clinical forms of glaucomas > 9.2 Primary open angle glaucomas)
11.8 Neuroprotection (Part of: 11 Medical treatment)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
