BDNF enhances retinal ganglion cell survival in cats with optic nerve damage

PURPOSE, TO determine whether brain-derived neurotrophic factor (BDNF), a n europrotectant in the small rat eye, might also serve as an effective neuro protectant in larger vertebrate eves. METHODS. A cat optic nerve crush model was combined with standard histologi c staining and analysis techniques. Twenty nine animals were studied, with the noninjected eye serving as the control eye. RESULTS. No treatment, or intravitreal injection of sterile water. resulted in an approximately 50% loss of ganglion cells 1 week after nerve crush. B y contrast, the mean percentages of surviving ganglion cells measured in ev es receiving injections of 15, 30, 60. and 90 mug BDNF at the time of the n erve damage were 52%, 81%. 77%, and 70%, respectively. Similar values were obtained for ganglion cell density. Cell size measurements suggest a comple x response among the different classes of cat ganglion cells; 30 mug BDNF t reatment retained the highest number of large ganglion cells, whereas 90 mu g minimized the loss of medium-sized neurons and retained normal proportion s of large, medium, and small ganglion cells, CONCLUSIONS. The data show that BDNF is an effective neuroprotectant in pri mate-sized eyes after optic nerve injury. Although the amount required to a chieve neuroprotection is much greater than that needed for the small rat e ye (30 mug versus 0.5 mug), when differences in vitreal volume are consider ed, the effective dose is similar (0.01 mug BDNF/mul vitreal volume). High doses of BDNF induce inflammation and result in a decrease in total ganglio n cell survival but appear necessary to save medium-sized neurons. which ar e affected most severely by nerve injury.