Retinal transplantation-induced recovery of retinotectal visual function in a rodent model of retinitis pigmentosa.
OBJECTIVE
To map the spatiotemporal decline in retinally driven activity in the superior colliculus (SC) of transgenic S334ter-line-3 rats that express a mutated rhodopsin, which causes photoreceptor degeneration. To determine whether transplantation of fetal retinal sheets into the subretinal space of these rats can recover visual activity in the SC.


METHODS
A visual stimulus was presented to the eye, and responses were recorded across the SC of untreated S334ter-line-3 rats aged 28 to 288 days. These data were used to draw a map of the developing scotoma. Intact retinal sheets from embryonic day 19 rats were transplanted into the subretinal space of S334ter-line-3 rats between 21 and 28 days of age. Responses to retinal stimulation were mapped in the SC of transplanted and sham control rats 78 to 163 days after surgery. The morphology of the retinas in all groups was examined.


RESULTS
Photoreceptor cell loss in untreated rats matched the decline in visual activity in the SC. At 28 days, there was a scotoma in the area of the SC that represents the central retina and, by 63 days, it had enlarged to cover the entire retinal representation. Visual responses were evoked in 64% of rats with retinal transplants. These retinally driven responses were confined to a small, contiguous region of the SC that represents the sector of the retina where the transplant was placed. Visual responses were absent in the SC outside this area in transplant recipients and throughout the SC of untreated and sham control rats.


CONCLUSIONS
Transplantation of fetal retinal sheets induced recovery of visual activity in the SC in this model of RP. The mechanisms underlying this functional recovery remain to be resolved, but these results suggest that transplantation should be further explored as a therapy for RP.
Sagdullaev
Botir T
BT
Department of Psychological and Brain Science, University of Louisville, Louisville, Kentucky 40292, USA.
Aramant
Robert B
RB
Seiler
Magdalene J
MJ
Woch
Gustaw
G
McCall
Maureen A
MA
D000818:Animals; D030801:Animals, Genetically Modified; D019393:Arrestin / Q000378:metabolism; D004195:Disease Models, Animal; D004594:Electrophysiology; D004596:Electroretinography; D005074:Evoked Potentials, Visual; D016332:Fetal Tissue Transplantation; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D020127:Recovery of Function; D012160:Retina / Q000637:transplantation*; D012174:Retinitis Pigmentosa / Q000503:physiopathology* / Q000601:surgery*; D013477:Superior Colliculi / Q000502:physiology*; D014785:Vision, Ocular / Q000502:physiology*; D014794:Visual Fields
D019393:Arrestin