H Chen1, A J Weber. 1. Department of Physiology, Michigan State University, East Lansing 48824, USA.
Abstract
PURPOSE: To determine whether brain-derived neurotrophic factor (BDNF), a neuroprotectant in the small rat eye, might also serve as an effective neuroprotectant in larger vertebrate eyes. METHODS. A cat optic nerve crush model was combined with standard histologic 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. By contrast, the mean percentages of surviving ganglion cells measured in eyes receiving injections of 15, 30, 60, and 90 microg BDNF at the time of the nerve damage were 52%, 81%, 77%, and 70%, respectively. Similar values were obtained for ganglion cell density. Cell size measurements suggest a complex response among the different classes of cat ganglion cells; 30 microg BDNF treatment retained the highest number of large ganglion cells, whereas 90 microg minimized the loss of medium-sized neurons and retained normal proportions of large, medium, and small ganglion cells. CONCLUSIONS: The data show that BDNF is an effective neuroprotectant in primate-sized eyes after optic nerve injury. Although the amount required to achieve neuroprotection is much greater than that needed for the small rat eye (30 microg versus 0.5 microg), when differences in vitreal volume are considered, the effective dose is similar (0.01 microg BDNF/microl vitreal volume). High doses of BDNF induce inflammation and result in a decrease in total ganglion cell survival but appear necessary to save medium-sized neurons, which are affected most severely by nerve injury.
PURPOSE: To determine whether brain-derived neurotrophic factor (BDNF), a neuroprotectant in the small rat eye, might also serve as an effective neuroprotectant in larger vertebrate eyes. METHODS. A cat optic nerve crush model was combined with standard histologic 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. By contrast, the mean percentages of surviving ganglion cells measured in eyes receiving injections of 15, 30, 60, and 90 microg BDNF at the time of the nerve damage were 52%, 81%, 77%, and 70%, respectively. Similar values were obtained for ganglion cell density. Cell size measurements suggest a complex response among the different classes of cat ganglion cells; 30 microg BDNF treatment retained the highest number of large ganglion cells, whereas 90 microg minimized the loss of medium-sized neurons and retained normal proportions of large, medium, and small ganglion cells. CONCLUSIONS: The data show that BDNF is an effective neuroprotectant in primate-sized eyes after optic nerve injury. Although the amount required to achieve neuroprotection is much greater than that needed for the small rat eye (30 microg versus 0.5 microg), when differences in vitreal volume are considered, the effective dose is similar (0.01 microg BDNF/microl vitreal volume). High doses of BDNF induce inflammation and result in a decrease in total ganglion cell survival but appear necessary to save medium-sized neurons, which are affected most severely by nerve injury.
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