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Temporary retinal ischemia in the rat leads to a proliferation of endothelial cells and glial cells. We tested the hypothesis that this proliferation is caused by a release of soluble mitogens from the ischemic retina. Conditioned media were prepared from normal rat retina and from retina that had undergone 2 h ischemia and 48 h reperfusion, at which time it showed intense mitotic activity. The conditioned media were placed in cultures of fibroblasts, bovine adrenal capillary endothelial cells, and rat brain astrocytes. Cell proliferation in vitro was stimulated by the retinal extracts in all cell cultures. However, the cell proliferation in cultures with conditioned media from normal retina was similar to that in cultures with conditioned media from ischemic and proliferating retina. Although these data are consistent with the presence of soluble growth factors in the retina, they also indicate that release of these growth factors into the surrounding milieu after transient retinal ischemia is not altered to a degree that would explain the dramatic increase in mitosis.

We developed a quantitative histologic method for assessing injury in the rat retina due to transient ischemia. We used this technique to test the effectiveness of local hypothermia and allopurinol, an inhibitor of oxygen-free radical formation, in reducing ischemia/reperfusion injury in the rat retina. Retinal ischemia and reperfusion was produced by transient ligation of the optic nerve. Histologic evaluation by a masked observer was based on the average count of nonpyknotic nuclei in the inner nuclear layer of the retina from eight high power fields (X100) in one 5 microns thick sagital section at or near the optic nerve. A sharp increase in tissue damage occurs between 90 and 120 min of ischemia. Ischemia for periods of 60 and 90 min produced mild damage while periods of 120 and 240 min produced severe damage. Hypothermia protected the retina significantly from 120 min of ischemic injury (P less than 0.001 student t-test, compared to 120 min control), while allopurinol had no protective effect.