Chronology of optic nerve head and retinal responses to elevated intraocular pressure.
OBJECTIVE
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.
Johnson
E C
EC
Kenneth C. Swan Ocular Neurobiology Laboratory, Casey Eye Institute, Oregon 97201, USA. johnsoel@ohsu.edu
Deppmeier
L M
LM
Wentzien
S K
SK
Hsu
I
I
Morrison
J C
JC
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D018031:Connexin 43 / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D053938:DNA Fragmentation; D017629:Gap Junctions; D007124:Immunoenzyme Techniques; D007429:Intraocular Pressure; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology*; D009414:Nerve Growth Factors / Q000378:metabolism; D009798:Ocular Hypertension / Q000378:metabolism / Q000473:pathology*; D009898:Optic Disk / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011914:Rats, Inbred BN; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology*
D019208:Brain-Derived Neurotrophic Factor; D018031:Connexin 43; D003598:Cytoskeletal Proteins; D009414:Nerve Growth Factors; C071951:neurotrophin 5; C073922:neurotrophin 4