TY - JOUR
T1 - Chronology of optic nerve head and retinal responses to elevated intraocular pressure
AU - Johnson, Elaine C.
AU - Deppmeier, Lisa M.H.
AU - Wentzien, Susan K.F.
AU - Hsu, Immanuel
AU - Morrison, John C.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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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M3 - Article
C2 - 10670473
AN - SCOPUS:0033950441
SN - 0146-0404
VL - 41
SP - 431
EP - 442
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 2
ER -