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Elaine C. Johnson, Lisa M. H. Deppmeier, Susan K. F. Wentzien, Immanuel Hsu, John C. Morrison; Chronology of Optic Nerve Head and Retinal Responses to Elevated Intraocular Pressure. Invest. Ophthalmol. Vis. Sci. 2000;41(2):431-442.
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purpose. To determine the chronology of optic nerve head and retinal responses
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
labeling alterations and for ganglion cell DNA fragmentation.
results. Mean IOP for the experimental eyes was 36 ± 8 mm Hg, an
approximately 15-mm Hg elevation above normal values. By 7 days of
pressure elevation above 40 mm Hg, endogenous immunostaining for
brain-derived neurotrophic factor and neurotrophin 4/5 was absent from
the nerve head and superior retina, 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 gap 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 degeneration, loss of
astrocytic glial fibrillary acidic protein staining, and 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 depletion of
endogenous neurotrophins, are readily identified in the rat eye after
experimental IOP elevation. However, the apparent chronology of these
responses suggests that the withdrawal of neurotrophic support was not
the only determinant of retinal ganglion cell apoptosis and axonal
degeneration in response to pressure.
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