Chronology of optic nerve head and retinal responses to elevated intraocular pressure

PURPOSE. TO determine the chronology of optic nerve head and retinal respon ses to elevated intraocular pressure (IOP). METHODS. After 1 to 39 days of unilaterally elevated IOP, experimental and fellow rat eyes were examined for morphology and immunohistochemical labeli ng alterations and for ganglion cell DNA fragmentation. RESULTS. Mean IOP for the experimental eyes was 36 +/- 8 mm Hg, an approxim ately 15-mm Hg elevation above normal values. By 7 days of pressure elevati on above 40 mm Hg, endogenous immunostaining for brain-derived neurotrophic factor and neurotrophin 4/5 was absent from the nerve head and superior re tina, whereas normal labeling was present in the inferior retina and distal optic nerve of these same eyes. These changes were preceded by a loss of g ap junctional connexin43 labeling and astrocytic proliferation in the nerve head and by increased retinal ganglion cell layer apoptosis in the retina. Nerve head depletion of neurotrophins coincided with evidence of axonal de generation, loss of astrocytic glial fibrillary acidic protein staining, an d spread of collagen VI vascular immunolabeling. After longer durations at these same pressures, neurotrophin labeling returned to nerve head glia and scattered retinal ganglion cells. CONCLUSIONS. Optic nerve head and retinal responses, including the depletio n of endogenous neurotrophins, are readily identified in the rat eye after experimental IOP elevation, However, the apparent chronology of these respo nses suggests that the withdrawal of neurotrophic support was not the only determinant of retinal ganglion cell apoptosis and axonal degeneration in r esponse to pressure.