The development a new glaucoma model and the identification of the factors inducing glaucomatous neuropathy

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In this study, we first tried to develop a new glaucoma model rat by transferring the cytotoxic gene to the trabecular meshwork, a main structure in the outflow system of aqueous humor. We employed HVJ envelope vector, a hybrid vector which has been reported to deliver the target gene in an efficient and a safe manner. We injected the HVJ envelope vector, containing the plasmid DNA which is subcloned reporter gene under the CMV promoter, into the anterior chamber of rats. During the period of 4 weeks after injection, there was no significant expression of reporter gene in the trabecular meshwork, compared to control eyes. To find a reliable glaucoma model, we made several kinds of glaucoma model rat and found out that the episcleral vein occulusion could induce chronic ocular hypertension with little surgical damage. Episcleral vein occulusion model showed the 30% decrease in number of retinal ganglion cells(RGCs) at 12 weeks after treatment, and the loss of RGCs and the cupping of optic disc were more significant at 30 weeks after treatment. There observed no gross changes in other retinal neurons, while Muller glia expressed the markers that indicate the reactive condition. During the early phase of IOP elevation, astrocytes within the optic nerve showed the increased expression of caspase 3, a marker for cell death, preceding the decrease in number of astrocytes. Microarray analysis for optic disc at 12 weeks after treatment, revealed that some of the genes involved in the cell adhesion, the formation of extracellular matrix, the regulation of cell cycle, were affected and the intensive study to find the factors to induce glaucomatous neuropathy is underway.