PURPOSE: The selective alpha-2 agonist brimonidine was used as a pharmacological probe to activate alpha 2 receptor-mediated neuroprotective signaling pathways and quantitate the enhancement of retinal ganglion cell survival and function in animals with ischemic retinal and optic nerve injury. METHODS: Two animal models were used to achieve different methods of neuronal insult. The first model involved mechanical injury of the rat optic nerve after treatment with a single intraperitoneal (i.p.) dose of brimonidine or a control vehicle. The second model involving acute retinal ischemic/reperfusion injury was used in a variety of experiments in which rats were treated with either intraperitoneal brimonidine or single dose topical brimonidine at various strengths. In all cases retinal ischemia was induced and maintained followed by reperfusion. In some cases, TUNEL staining was performed on histologic sections of the retinas of rats that had been sacrificed after 24 hours. To examine the activation of neuronal survival pathways at the molecular level, rats were injected with i.p. brimonidine followed by the isolation of mRNAs from whole retinas 24 hours after ischemic injury. RESULTS: Intraperitoneal brimonidine enhanced rat RGC survival and function in the partial crush injury model, and neuroprotection was dose-dependent. Topical application of brimonidine 1 hour before injury was effective in decreasing ischemic retinal injury. Ischemic retinas treated with brimonidine resulted with a large decrease in TUNEL staining. CONCLUSIONS: Treatment with the alpha 2 adrenoreceptor agonist brimonidine was found to confer neuroprotection to retinal ganglion cells in two distinct models of neuronal injury resulting from acute retinal ischemia/reperfusion and calibrated optic nerve compression.
PURPOSE: The selective alpha-2 agonist brimonidine was used as a pharmacological probe to activate alpha 2 receptor-mediated neuroprotective signaling pathways and quantitate the enhancement of retinal ganglion cell survival and function in animals with ischemic retinal and optic nerve injury. METHODS: Two animal models were used to achieve different methods of neuronal insult. The first model involved mechanical injury of the rat optic nerve after treatment with a single intraperitoneal (i.p.) dose of brimonidine or a control vehicle. The second model involving acute retinal ischemic/reperfusion injury was used in a variety of experiments in which rats were treated with either intraperitoneal brimonidine or single dose topical brimonidine at various strengths. In all cases retinal ischemia was induced and maintained followed by reperfusion. In some cases, TUNEL staining was performed on histologic sections of the retinas of rats that had been sacrificed after 24 hours. To examine the activation of neuronal survival pathways at the molecular level, rats were injected with i.p. brimonidine followed by the isolation of mRNAs from whole retinas 24 hours after ischemic injury. RESULTS: Intraperitoneal brimonidine enhanced rat RGC survival and function in the partial crush injury model, and neuroprotection was dose-dependent. Topical application of brimonidine 1 hour before injury was effective in decreasing ischemic retinal injury. Ischemic retinas treated with brimonidine resulted with a large decrease in TUNEL staining. CONCLUSIONS: Treatment with the alpha 2 adrenoreceptor agonist brimonidine was found to confer neuroprotection to retinal ganglion cells in two distinct models of neuronal injury resulting from acute retinal ischemia/reperfusion and calibrated optic nerve compression.
Authors: T Aung; F T S Oen; H-T Wong; Y-H Chan; B-K Khoo; Y-P Liu; C-L Ho; J See; L H Thean; A C Viswanathan; S K L Seah; P T K Chew Journal: Br J Ophthalmol Date: 2004-01 Impact factor: 4.638