Nerve growth factor promotes functional recovery of retinal ganglion cells after ischemia.

PURPOSE

To investigate the effect of a transient complete ischemia on the function of cat retina and to determine whether nerve growth factor (NGF), which was previously shown to enhance retinal ganglion cell (RGC) survival after optic nerve section in the adult rat, can promote recovery of retinal neurons after the ischemic insult.

METHODS

Function of distal and proximal retina was assessed by recording the electroretinogram in response to both homogeneous flickering light (FERG) and contrast reversing gratings (PERG), respectively, 30 days after the induction of a 60-minute episode of ischemia. Visual evoked potentials in response to contrast reversing gratings were also recorded to evaluate visual acuity and contrast thresholds. Cell survival after ischemia was assessed in retinal whole-mounts stained with cresyl violet. Cats were intraocularly treated with NGF every other day, 3 times a week, for 30 days. Controls were treated with either phosphate buffered saline or cytochrome c.

RESULTS

After ischemia, the FERG was not significantly affected. On the contrary, the PERG, visual acuity, and contrast thresholds were severely impaired. After NGF treatment, PERG response amplitudes were much less reduced compared to controls, and visual acuity and contrast thresholds were virtually normal. In addition, a larger number of presumed RGCs was present in the NGF-treated retinas compared to the cyt c-treated ones.

CONCLUSIONS

The more proximally located retinal neurons, in particular RGCs, are highly vulnerable to ischemia. Intraocular NGF treatment was effective in enhancing the survival and functional recovery of these neurons. This suggests that NGF may represent a novel therapeutic agent for the treatment of ischemic ocular pathologies.