[The dawn of neuroprotective therapy for glaucomatous optic neuropathy].

BACKGROUND

Neuroprotective therapy for glaucoma can be defined as treatment of the recalcitrant disease via direct modification of the molecular mechanism involving retinal ganglion cell death. I and my collaborators, at the dawn of the neuroprotective era, elaborated and conducted the following investigations in order to pursue our final goal, i.e., substantial improvement of the quality of life of glaucoma patients.

METHODS AND RESULTS

1. Investigation of in traocular pressure (IOP) independent prognostic factors in glaucomatous optic neuropathy. Clinical investigation along with multivariate analyses revealed that some IOP-independent factors including optic disc hemorrhage and compromised retrobulbar hemodynamics are associated with the development and progression of glaucomatous optic neuropathy. 2. Glaucoma therapy other than ocular hypotensive therapy. A long-term follow-up study demonstrated that calcium-channel blockers are efficacious in stabilizing the visual field in normal-tension glaucoma. 3. Establishment of animal models for glaucomatous optic neuropathy. Experimental animal models were created to conduct neuroprotective research for glaucomatous optic neuropathy: an IOP elevation model and an optic nerve crush model in the rat. In addition, a system was constructed for electrophysiological study in the rat to quantitatively investigate neuroprotective effect on the retina and the optic nerve. 4. Neuroprotective effects of several agents on experimental optic neuropathies. Several agents were studied for their neuroprotective effects on optic neuropathies induced in the rat. Some apoptosis-modifying agents were found to possess neuroprotective effects against optic neuropathy.

CONCLUSIONS

IOP-independent prognostic factors exist in glaucomatous optic neuropathy. Glaucomatous optic neuropathy can be stabilized by IOP-unrelated therapy like calcium-channel blockers, at least in a subset of the disease. Modification of the apoptosis mechanism can protect retinal ganglion cells from damage caused by optic neuropathy in the rat models. All of the present studies suggest that neuroprotective therapy will probably become the treatment of choice in the near future for glaucomatous optic neuropathy.