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Wolfgang Radner, Srinivas R. Sadda, Mark S. Humayun, Satoshi Suzuki, Michelle Melia, James Weiland, Eugene de Juan; Light-Driven Retinal Ganglion Cell Responses in Blind rd Mice after Neural Retinal Transplantation. Invest. Ophthalmol. Vis. Sci. 2001;42(5):1057-1065.
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purpose. Light-elicited retinal ganglion cell (RGC) responses after fetal neural
retinal transplantation have not been demonstrated in animal or human
subjects blind from outer retinal degeneration, despite apparent
morphologic success. This study was designed to test the hypothesis
that the functional success of retinal transplantation may be enhanced
by using a young host retina (13 days old).
methods. At postnatal day (P)13 C3H/HeJ (rd/rd) retinal
degenerate mice received a subretinal transplant, in one eye only, of
neural retinal tissue isolated from newborn normal C57/BL6J mice.
Between 33 and 35 days after transplantation, local electroretinograms
(ERGs) and ganglion cell responses were recorded directly from the
retinal surface using a differential bipolar surface electrode.
Measurements were performed both with and without light stimulation.
Similar recordings were also performed in age-matched eyes subjected to
sham transplantation, in control eyes that were not subjected to
surgery, and in animals eyes that underwent transplantation at 8 weeks
of age. After the recordings, the eyes were processed for light and
transmission electron microscopy.
results. Three of 10 mice showed bursts of ganglion cell action potentials (ON
response only) as well as recordable intraocular ERGs over the
transplant in response to 1-second and 200-msec light stimuli.
Light-driven ganglion cell responses could not be recorded in areas
outside the transplant in all transplant-recipient eyes, age-matched
control eyes, and sham-transplantation eyes. Light responses also could
not be recorded in animal eyes that received transplants at an older
age (8 weeks). Electron microscopic examination confirmed the presence
of photoreceptor outer segments in the areas affected by
conclusions. This study demonstrates the presence of light-driven ganglion cell
responses after subretinal transplantation in a retinal degenerate
model. This finding may reflect functional integration of the
transplant with the host, but a rescue effect on remaining host
photoreceptors cannot be ruled out. The findings suggest, however, that
modification of host parameters, such as host age, may be important
approaches for improving the functional success of retinal
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