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A. J. Weber, C. Ramanathan, S. Viswanathan, C. Harman; Combined BDNF Application to the Eye and Brain Enhances Ganglion Cell Survival and Function in the Cat Following Optic Nerve Injury. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4062.
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© ARVO (1962-2015); The Authors (2016-present)
Previously we showed that BDNF not only is a potent neuroprotectant, but also that it preserves the dendritic integrity and visual responses of cat ganglion cells following optic nerve injury. While these studies treated the eye alone, the aim here was to examine whether dual treatment of the eye and brain might yield an even greater neuroprotective effect.
36 cats received a partial crush of one optic nerve and either no treatment (NT), treatment of the injured eye with 90µg BDNF at the time of the crush, or treatment of the injured eye combined with continuous delivery of BDNF to both visual cortices via osmotic minipumps (6µl/day;0.3µg/µl). After 1wk or 2wk survival periods, pattern electroretinograms (PERG) were obtained under ketamine-xylazine anesthesia. The retinae then were fixed, whole-mounted, stained, and ganglion cell counts obtained.
Ganglion cell survivals for each condition relative to the normal eyes were: NT:1wk=51%;2wk=48%; Eye alone:1wk=66%; 2wk=78%;Eye+Cortex:1wk=96%;2wk=92%. ANOVA (p=0.05) indicated significant increases in cell survival with respect to NT for each treatment condition, and between conditions, but not across survival times. Mean PERG response amplitudes for animals receiving treatment were significantly greater than those measured in the NT eyes, and not different from the control eye responses, with the exception of the 2wk, eye treatment only, animals that showed responses intermediate to the control and NT eyes (students t-test;p=0.05).
Application of BDNF to both the eye and brain following optic nerve injury results in a significant increase in ganglion cell survival relative to treatment of the eye alone. Functionally, the single and dual treatment strategies are equally beneficial over the first week post-injury, however, with longer post-injury periods, the dual treatment approach provides the greater benefit. These studies suggest a need to ‘think outside the eye’ with respect to the development of neuroprotection strategies aimed at preserving retinal structure and function in glaucoma and other visual disorders.
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