Light-driven retinal ganglion cell responses in blind rd mice after neuralretinal transplantation

PURPOSE. Light-elicited retinal ganglion cell (RGC) responses after fetal n eural retinal transplantation have not been demonstrated in animal or human subjects blind from outer retinal degeneration, despite apparent morpholog ic success. This study was designed to test the hypothesis that the functio nal success of retinal transplantation may be enhanced by using a young hos t retina (13 days old). METHODS. At postnatal day (P)13 C3H/HeJ (rd/rd) retinal degenerate mice rec eived a subretinal transplant, in one eye only, of neural retinal tissue is olated from new-born normal C57/BLbJ mice. Between 33 and 35 days after tra nsplantation, local electroretinograms (ERGs) and ganglion cell responses w ere 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 su bjected 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 transmissi on 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 transpla nt in response to 1-second and 200-msec light stimuli. Light-driven ganglio n cell responses could not be recorded in areas outside the transplant in a ll transplant-recipient eyes, age-matched control eyes, and sham-transplant ation eyes. Light responses also could not be recorded in animal eyes that received transplants at an older age (8 weeks). Electron microscopic examin ation confirmed the presence of photoreceptor outer segments in the areas a ffected by transplantation. CONCLUSIONS. This study demonstrates the presence of light-driven ganglion cell responses after subretinal transplantation in a retinal degenerate mod el. This finding may reflect functional integration of the transplant with the host, but a rescue effect on remaining host photoreceptors cannot be ru led out. The findings suggest, however, that modification of host parameter s, such as host age, may be important approaches for improving the function al success of retinal transplantation.