Preservation of visual responsiveness in the superior colliculus of RCS rats after retinal pigment epithelium cell transplantation.
The dystrophic RCS rat undergoes progressive photoreceptor degeneration due to a primary defect in retinal pigment epithelial (RPE) cells. This has a major impact on central visual responsiveness. Here we have examined how functional deterioration is contained by subretinal transplantation of immortalized human RPE cells. Transplantation was done at three to four weeks of age prior to significant photoreceptor loss and recipients were kept on cyclosporin. At six months of age, sensitivity maps and multi-unit response properties were obtained across the visual field by recording at 76 equidistant sites encompassing the whole superior colliculus.A significant degree of functional protection, both in terms of area of responsive retina and response characteristics was observed following RPE transplantation. At best, the sensitivity, latency of onset, and response rise time were all maintained within normal ranges and this was achieved with no more than half of the normal complement of photoreceptors. Although partial, the degree of anatomical preservation (both in terms of outer nuclear layer thickness and area of rescue) correlated well with the level of preserved visual sensitivities. Sham injections also resulted in rescue, though the area of preservation was strictly confined to the needle injury site and the response properties were significantly worse than with RPE injections. This study shows that central physiological responsiveness and correlated retinal morphology can be preserved in an animal model of retinal disease by implantation of an immortalized cell line. The use of retinal sensitivity measurements provides a background for assessing higher visual functions in these animals and a direct comparison for human perimetry measures.
Sauvé
Y
Y
Moran Eye Center, University of Utah Health Sciences Center, 50 North Medical Drive, Salt Lake City, UT 84132, USA. yves.sauve@hsc.utah.edu
Girman
S V
SV
Wang
S
S
Keegan
D J
DJ
Lund
R D
RD
D000200:Action Potentials / Q000235:genetics; D000818:Animals; D016380:Brain Tissue Transplantation / Q000379:methods*; D002461:Cell Line, Transformed; D004195:Disease Models, Animal; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D009410:Nerve Degeneration / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D010775:Photic Stimulation; D010786:Photoreceptor Cells / Q000473:pathology / Q000503:physiopathology; D010857:Pigment Epithelium of Eye / Q000503:physiopathology / Q000637:transplantation*; D051381:Rats; D011922:Rats, Mutant Strains; D011930:Reaction Time / Q000502:physiology; D020127:Recovery of Function / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000473:pathology / Q000502:physiology; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D013477:Superior Colliculi / Q000502:physiology*; D013997:Time Factors; D016896:Treatment Outcome; D014795:Visual Pathways / Q000473:pathology / Q000503:physiopathology; D014796:Visual Perception / Q000502:physiology*