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Hao Chen, Arthur J. Weber; BDNF Enhances Retinal Ganglion Cell Survival in Cats with Optic Nerve Damage. Invest. Ophthalmol. Vis. Sci. 2001;42(5):966-974.
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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 μg 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 μg BDNF treatment retained the highest number
of large ganglion cells, whereas 90 μg 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 μg versus 0.5 μg), when differences in
vitreal volume are considered, the effective dose is similar (0.01 μg
BDNF/μl 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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