Invest Ophthalmol Vis Sci 2010 Dec 30;51(12):6688-99. Epub 2010 Jun 30.
Department of Experimental Ophthalmology, School of Medicine, University Eye Hospital Münster, Münster, Germany.
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Invest Ophthalmol Vis Sci 2008 Oct 19;49(10):4515-22. Epub 2008 Jun 19.
Department of Biological Sciences, Allergan Pharmaceuticals, Irvine, California 92612, USA.
Purpose: alpha2 Agonists, such as brimonidine, have been shown to protect retinal ganglion cells (RGCs) in animal models of glaucoma and acute retinal ischemia. In this study, the authors investigated the neural mechanism that may underlie alpha2 neuroprotection of RGCs.
Methods: The authors used in situ RGCs in the isolated rat retina to investigate possible interactions between alpha2 and N-methyl-D-aspartate (NMDA) receptors and rat glaucoma or rabbit retinal NMDA excitotoxicity models to verify in vitro findings under in vivo conditions. Read More
Invest Ophthalmol Vis Sci 1999 Jan;40(1):65-73
Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
Purpose: The neurodegenerative progression of glaucoma is considered to be related not only to primary risk factors such as the elevation of intraocular pressure, but also to mediators of secondary neuronal degeneration. In the present study, the neuroprotective activity of the alpha2-adrenoreceptor agonists brimonidine, AGN 191103, and clonidine were examined in an animal model that simulates secondary neuronal degeneration of the optic nerve in a way thought to be independent of elevation of intraocular pressure. The beta-blocker timolol, currently used clinically to decrease intraocular pressure, was also examined for neuroprotective activity at dosages corresponding to the effective antihypertensive dosage. Read More
Invest Ophthalmol Vis Sci 2005 Sep;46(9):3177-87
Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Kentucky Lions Eye Center, 301 E. Muhammad Ali Boulevard, Louisville, KY 40202, USA.
Purpose: Based on the evidence of an amplified production of reactive oxygen species (ROS) during glaucomatous neurodegeneration, proteomic analysis was performed to determine oxidative modification of retinal proteins after experimental elevation of intraocular pressure (IOP).
Methods: IOP elevation was induced in rats by hypertonic saline injections into episcleral veins. Protein expression was determined by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) of retinal protein lysates obtained from eyes matched for the cumulative IOP exposure and axon loss. Read More
Surv Ophthalmol 2001 May;45 Suppl 3:S290-4; discussion S295-6
Department of Biological Sciences, Allergan, Inc., Irvine, CA 92612, USA.
The loss of retinal ganglion cells (RGCs) in glaucoma occurs progressively over many years. A neuroprotective drug should enhance survival of RGCs in the presence of chronic stress/injury. Four criteria are proposed for assessing the likely therapeutic utility in human glaucoma of drugs that have demonstrated neuroprotective activity in animal models: 1) A specific receptor target must be in the retina/optic nerve; 2) Activation of the target must trigger pathways that enhance a neuron's resistance to stress/injury and/or suppresses toxic insults; 3) The drug must reach the retina/vitreous at pharmacologic doses; and 4) The neuroprotective activity should be demonstrated in clinical trials. Read More