Abstract
Abstract: :
Purpose: Neurotech S.A. is developing cell-based therapies for the treatment of ophthalmic disorders with a special interest in retinal degeneration. One of the Company's strategies consists of transplanting well-characterized viable human retinal pigment epithelium (RPE) cells into the subretinal space in order to replace dysfunctional endogenous RPE cells. The proof of efficacy of this approach has been demonstrated recently in the Royal College of Surgeons (RCS) rat modela. In the present study, we examined whether or not the immortalized human RPE cell line NTC-200 could rescue photoreceptors when injected into the subretinal space of dystrophic RCS rats. In addition, the visual performance of the treated rats was assessed. Methods: Three-week-old pigmented dystrophic RCS rats were treated under general anesthesia by a unilateral injection of 2x105 cultured NTC-200 cells (2 µl) into the temporal superior subretinal space using a trans-scleral approachb. Sham-treated dystrophic RCS rats received a unilateral subretinal injection of 2 µl graft medium. All rats remained under cyclosporin regimen throughout the test period. At the age of 12 weeks, all rats were subjected to optokinetic reflex testings using the spatial grating frequency of 0.5 cycles/degreec. Subsequently, the rats were sacrificed for histology and photoreceptor nuclei counting. Results: The presented behavioral and anatomical data reveal an association between the response to the presented grating stimulus and the photoreceptor rescue. These results confirm anatomical and functional data obtained earlier with other cell linesa or factorsd. Conclusion: NTC-200-mediated delay or slowing of the deterioration of the rats' visual performance is associated with photoreceptor rescue. a Lund et al. (2001) Proc. Natl. Acad. Sci. USA 98(17):9942-9947, Coffey et al. (2001) Nat. Neurosci., in press. b All animal experiment procedures conform to NIH guidelines. c Cowey & Franzini (1979) Exp. Brain Res. 35:443-455. d Whiteley et al. (2001) ARVO poster #3392.
Keywords: 607 transplantation • 567 retinal pigment epithelium • 308 age-related macular degeneration