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

Purpose To determine the morphological and immunohistochemical response of the eye to elevated intraocular pressure (HOP) Methods Episcleral injections of hypertonic saline were used to produce sustained unilateral l IOP in 22 rats Results Mean IOP in experimental eyes ranged from 3 to 28 mm Hg above the fellow eye. While no alterations were seen in globe sections examined after |_day of r IOP, beginning at 3 days, changes in protein localization occurred in the optic nerve head The gap junction protein, connexin-43, was lost from the nerve head transition and neck region nerve fiber bundles while glial column proliferating cell nuclear antigen (PCNA) labeling appeared. At one week, apparent collagen VI staining of vasculature in the nerve head increased In eyes with >10 mmHg mean HOP, nerve head glial column nuclear rearrangement was dramatic, with a corresponding decrease in glial fibrillary acidic protein staining Axonal retraction bulbs labeled by neurofilament proteins antibodies were prominent Superior retinal staining intensity diminished for the neurotrophins BDNF, NT 4/5, and TGF, while nerve fiber layer FGF label intensified After 2 weeks of HOP> 10 mmHg, retinal ganglion cell soma labeling for GAP-43 and phosphorylated neurofilaments first appeared. Axonal retraction bulbs and nuclear staining for c-jun and PCNA appeared to move distally in the oplic nerve. These morphological and immunohistochemical alterations developed more slowly in eyes exposed to lower mean 1 lOPs. Conclusions. Immunohistochemica! and morphological alterations following HOP in the rat eye appear first in the optic nerve head, with delayed responses in the retina and optic nerve.