gms | German Medical Science

Purpose: Retinal ischemia-reperfusion leads to evident changes in the retina. However, the global effect of ischemia on different retinal cells and the optic nerve has not been adequately investigated. The aim of this study was to assess changes in retina and optic nerve as a result of retinal ischemia-reperfusion to investigate possible mechanisms of neurodegeneration.

Methods: Ischemia-reperfusion (I/R) was induced by raising the intraocular pressure in one eye of rats to 140 mmHg for 1h (n=5/group). The other eye served as control. 21 days after ischemia the retinas and optic nerves were removed for immunohistology. Changes of RGCs, amacrine, rod bipolar, and glia cells were analyzed. In optic nerves the neurofilament, myelin basic protein and oligodendrocyte transcription factor 2 were analyzed. Following cell counts and area measurements, statistical analyses with student’s t-test were performed.

Results: A RGC decrease (p=0.0016) caused by apoptosis (p<0.001) was noted. Also, a loss of cholinergic amacrine cells (p<0.001) as well as an increase of GFAP+ area was detected in I/R retinas (p<0.001). No differences in regard to rod bipolar cells were noted. In optic nerves, neurofilament proteins showed significant degeneration in the I/R group (p<0.001) whereas the expression of the myelin protein was not significantly reduced. The number of oligodendrocytes was clearly diminished in I/R animals (p˂0.01).

Conclusions: We hypothesize that, although I/R is a global event, the inner retina is the primary site of damage after I/R followed by optic nerve degeneration. RGCs and amacrine cells seem to be affected first. We also assume that damage later spreads to the outer retina and also the axons. These secondary findings in the optic nerve, following a primary retinal lesion, may help elucidating possible pathophysiological mechanisms of neurodegeneration and allow to improve neuroprotective strategies.