Protection of the rat retina from ischemic injury by brain-derived neurotrophic factor, ciliary neurotrophic factor, and basic fibroblast growth factor.

PURPOSE

The protective effects of three survival-promoting agents on ischemia-induced retinal injury in the rat were investigated. The agents included brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and basic fibroblast growth factor (bFGF).

METHODS

Retinal ischemia was induced in Lewis albino rats by increasing intraocular pressure to 160 mm Hg for 90 minutes. The agents or buffer controls were injected intravitreally at different times, either before or after the ischemic insult, and the postischemic survival time was either 7 or 14 days. The degree of retinal damage was assessed from plastic-embedded sections by cytologic analysis, measurement of the thickness of several layers, and neuronal counts of the ganglion cell layer.

RESULTS

Retinal ischemia thinned and reduced cell numbers in the inner retinal layers, but not in the photoreceptor nuclear layer. Each agent transiently ameliorated the degenerative changes when it was injected 2 days before ischemia. At 7 days postischemia, the inner retinal layers were far less damaged, and more ganglion cells were present than in buffer-injected or uninjected eyes. The protective effect was no longer evident at 14 days postischemia, except in the inner nuclear layer of the BDNF-treated eyes. If a second injection of BDNF was made 5 days after the ischemic insult, then the inner retinal layers were more preserved than buffer controls at 14 days postischemia, but the survival of ganglion cells was not enhanced. A single injection of BDNF at either 1 or 3 days postischemia reduced the degree of inner retinal damage and increased the number of surviving ganglion cells over that in buffer-injected controls. (CNTF and bFGF were not studied with postischemic injections.)

CONCLUSIONS

BDNF, CNTF, and bFGF transiently protect the retina from pressure-induced ischemic injury when given 2 days before ischemia, and a second injection of BDNF given postischemically can prolong the protective effect. Moreover, protection afforded by BDNF can be seen even when applied only 1 or 3 days after the ischemic insult, although the protective effect is greater at 1 day than at 3 days postischemia.