Increased spontaneous retinal ganglion cell activity in rd mice after neural retinal transplantation

PURPOSE: To study the functional success of neural retinal transplantation by means of retinal surface ganglion cell recordings. METHODS: Eight-week-old C3H/HeJ (rd/rd) retinal degeneration mice received transplants (subretinal) in one eye only of neural retinal tissue isolated from newborn normal C57/BL6J mice. Four weeks after transplantation, ganglion cell responses were recorded directly from the retinal surface over the transplant, with a differential bipolar surface electrode. Measurements were performed, both with and without light stimulation. Similar recordings were performed in nontransplant areas of the transplant-recipient eyes, and in age-matched sham-treated and untreated control eyes. After the recordings, the eyes were processed for light and transmission electron microscopy. RESULTS: Histologic examination showed that in some areas, transplanted cells were organized into small sheets and differentiated into photoreceptors with outer segments in intimate contact with the host RPE. No light-driven ganglion cell responses were recordable from the transplant-recipient or control eyes. However, the spontaneous ganglion cell activity was higher in the transplant areas (mean: 10.8 +/-12.0 spikes/1.6 sec) compared with nontransplant areas of these recipient eyes (mean: 2.4 +/- 5.7spikes/1.6 sec; P < 0.001), sham-treated eyes (mean: 2.5 +/- 4.8 spikes/1.6 sec; P < 0.001), and the untreated control eyes (mean: 2.2 +/- 4.4 spikes/1.6 sec; P < 0.001). CONCLUSIONS: Subretinal transplantation of neural retinal tissue results in a local increase of spontaneous ganglion cell activity. The increased activity may be due to the release of neurochemically active substances as a result of the presence of the transplant. Although light responses were not recordable, the technique of retinal surface ganglion cell recording may be useful for assessing the functional success of transplantation.