Long-term vision rescue by human neural progenitors in a rat model of photoreceptor degeneration.
OBJECTIVE
As a follow-up to previous studies showing that human cortical neural progenitor cells (hNPC(ctx)) can sustain vision for at least 70 days after injection into the subretinal space of Royal College of Surgeons (RCS) rats, the authors examined how functional rescue is preserved over long periods and how this relates to retinal integrity and donor cell survival.


METHODS
Pigmented dystrophic RCS rats (n = 15) received unilateral subretinal injections of hNPC(ctx) at postnatal day (P) 21; control rats (n = 10) received medium alone and were untreated. All animals were maintained on oral cyclosporine A. Function was monitored serially by measuring acuity (using an optomotor test) and luminance thresholds (recording from the superior colliculus) at approximately P90, P150, and P280. Eyes were processed for histologic study after functional tests.


RESULTS
Acuity and luminance thresholds were significantly better in hNPC(ctx)-treated animals than in controls (P < 0.001) at all time points studied. Acuity was greater than 90%, 82%, and 37% of normal at P90, P150, and P270, whereas luminance thresholds in the area of best rescue remained similar the whole time. Histologic studies revealed substantial photoreceptor rescue, even up to P280, despite progressive deterioration in rod and cone morphology. Donor cells were still present at P280, and no sign of donor cell overgrowth was seen.


CONCLUSIONS
Long-term rescue of function and associated morphologic substrates was seen, together with donor cell survival even in the xenograft paradigm. This is encouraging when exploring further the potential for the application of hNPC(ctx) in treating retinal disease.
Wang
Shaomei
S
Casey Eye Institute, Oregon Health and Sciences University, Portland, Oregon 97239, USA.
Girman
Sergej
S
Lu
Bin
B
Bischoff
Nicholas
N
Holmes
Toby
T
Shearer
Rebecca
R
Wright
Lynda S
LS
Svendsen
Clive N
CN
Gamm
David M
DM
Lund
Raymond D
RD
D000818:Animals; D002470:Cell Survival; D006801:Humans; D007267:Injections; D008027:Light; D009474:Neurons / Q000637:transplantation*; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology; D051381:Rats; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology; D012162:Retinal Degeneration / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery*; D017948:Retinal Rod Photoreceptor Cells / Q000473:pathology; D012684:Sensory Thresholds; D033581:Stem Cell Transplantation / Q000379:methods; D013997:Time Factors; D014183:Transplantation, Heterologous; D014785:Vision, Ocular; D014792:Visual Acuity