Study on IOP-independent glaucoma treatment and pathogenetic mechanisms of glaucomatous optic neuropathy

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We first established two experimental models of glaucomatous optic neuropathy: one by intracameral Indian ink injection followed by laser irradiation to the chamber angle and the other by direct optic nerve damage with a clip. Using the models, several kinds of drugs were investigated in terms of possible neuroprotective effect on glaucomatous.optic neuropathy. Noncompetitive NMDA receptor antagonists, T-588, tacrolimus and betaxolol successfully showed neuroprotective effects on the models, which were confirmed by retinal ganglion cell counts, histopathology and electroretinogram measurement. These results suggest the possibility of IOP-independent glaucoma therapy by pharmacological modification of the apoptotic process.Another rat model for retinal ganglion cell apoptosis was created by thrombosis formation and reperfusion of the retinal arteries. Time-dependent apoptotic reaction was observed in the model, suggesting that the model might be used for investigation of glaucomatous optic neuropathy.We investigated lOP-independent factors for development and progression of glaucomatous optic neuropathy in a clinical setting. A multivariate analysis demonstrated several lOP-independent factors such as optic disc hemorrhage, peripapillary atrophy and abnormal orbital hemodynamics were associated with progression of glaucomatous optic neuropathy. Calcium-channel blocker treatment was associated with favorable prognosis of optic neuropathy.These results indicate the possibility of totally new treatment modalities for glaucoma other than currently used ocular hypotensive therapy.