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P. B. Yang, M. J. Seiler, R. B. Aramant, F. R. Yan, M. Mahoney, L. M. Kitzes, H. S. Keirstead; Improved Restoration of Visual Responses in the SC of Rats With Retinal Degeneration by BDNF- or GDNF-Treated Retinal Transplants. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6262.
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To investigate in a rat retinal degeneration model whether retinal transplant-induced restoration of visual responses in the superior colliculus (SC) can be improved by glial cell-line derived neurotrophic factor (GDNF), as well as brain-derived neurotrophic factor (BDNF).
Transgenic pigmented S334ter line 3 retinal degenerate rats (age 4-6 weeks) were subretinally implanted with BDNF or GDNF-microsphere-treated retinal progenitor sheets. Controls included non-treated retinal transplants, cortex transplants, sham surgeries, and age-matched normal and transgenic rats. Multi-unit responses were recorded from the SC following photic stimulation after overnight dark-adaptation. Response thresholds, spike counts, onset response latency, and magnitude of responses were evaluated.
The SC of degenerate rats with retinal transplants (age up to 45 weeks) responded to light in an area topographically corresponding to the placement of the transplant in the retina. The SC in sham control animals, degenerate rats without surgery, and rats with cortex transplants did not respond. However, the onset response latency and magnitude of response in degenerate rats with retinal transplants (with and without factors) did not vary as a function of stimulus intensity, in contrast to normal controls. Rats with BDNF or GDNF-treated transplants responded to photic stimulation at a lower luminance (-4.27 and -4.5 log cd/m2, respectively) than rats with transplants without treatment (-2.89 log cd/m2).
Compared to untreated transplants, the results suggest that retinal transplants treated with BDNF or GDNF not only restored visual responses but also enhanced the restoration of visual function as demonstrated by a lower luminance threshold.
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