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F Schuettauf, R Naskar, KM Quinto, D Zurakowski; Effects of Anti-glaucoma Medications on Gangion Cell Survival: The DBA/2J Mouse Model . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2186.
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Purpose: Although various investigators have reported elevated intraocular pressure and glaucomatous changes in DBA/2J mice, they have not explored whether conventional glaucoma therapy could retard the ganglion cell loss in these animals, nor have they attempted to quantify ganglion cell survival in this mouse strain. Accordingly, we sought to determine whether several agents either approved or undergoing trials in human glaucoma - are effective at preventing ganglion cell loss in the DBA/2J mouse. Methods: Adult DBA/2J mice were either treated with commercial eye-drops containing timolol , pilocarpine, brimonidine, or dorzolamide, or received intraperitoneal injections of the NMDA-receptor antagonist memantine. Surviving retinal ganglion cells (RGC) of treated and control mice were retrogradely labeled with fluorogold and counted on retinal whole mounts. Results: In treated mice, memantine and timolol significantly increased the number of surviving RGC. Animals injected with memantine had 2316 ± 627 cells/mm² and eyes treated with timolol had 2313 ± 767 cells/mm² surviving six months after treatment. In contrast, eyes of mice subjected to treatment with dorzolamide had 1894 ± 456 cells/mm², eyes treated with pilocarpine had 1670 ± 1071 RGC/mm² surviving at six months. Untreated DBA/2J mice had 1652 ± 1064 retinal ganglion cells/mm² at six months. Conclusions: It appears that the DBA/2J mouse may represent a promising candidate for further experimentation in glaucoma, inasmuch as the DBA/2J disease process develops spontaneously, and leads to ganglion cell loss in a time dependent fashion. Our studies demonstrate that this time-dependent loss of RGC can be inhibited by either conventional anti-glaucomatous therapy with b-Blockers or injections with an NMDA-receptor antagonist. Hopefully, future work will establish whether lowering the IOP in this model is associated with the preservation of ganglion cells.
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