Restoration of visual responses following transplantation of intact retinal sheets in rd mice

Abstract

Abstract: : Purpose: To correlate the functional outcomes with histologic findings following transplantation of fetal retinal sheets in rd mice, and to investigate the mechanisms of visual function restoration. Methods: Twenty one postnatal day 31–38 rd/rd (C3H/HeJ) mice were transplanted in one eye with retinal sheets (1.0 x 0.4 mm) obtained from embryonic day (E) 17 enhanced–green–fluorescent protein (eGFP) mice. Four to five weeks after transplantation, visual responses to a light flash were recorded across the superior colliculus (SC) in seven eyes of seven mice in which clear ocular media were present. Following the SC recording, the eyes were enucleated and processed for immunohistochemistry and examined using confocal microscopy. Results: In three out of the seven eyes (43%), positive responses were recorded in the SC in an area topographically corresponding to the placement of the transplant in the host retina. No responses were recorded in the untreated eyes of 5–week–old and 9–week–old rd/rd mice. In contrast, visual responses were recorded over the entire SC in normal eyes. The response onset latencies were similar to those of normal control mice. The organization of the graft did not appear to correlate as expected with the electrophysiology results, as eyes with well–organized, laminated grafts showed no response whereas the three light responsive eyes had rosetted or disorganized grafts. All three light responsive eyes demonstrated much higher levels of recoverin immunoreactivity in the host retina overlying the graft compared with untreated age–matched rd/rd mice. Conclusions: Restoration of the superior colliculus visual response does not appear to depend on a well–organized transplant in the rd/rd mouse. Increased recoverin staining in the host retina in light–responsive animals suggested that host cone rescue was the likely mechanism of vision restoration in this transplant model.

Keywords: transplantation • electrophysiology: non–clinical • degenerations/dystrophies