Subretinal transplantation of genetically modified human cell lines attenuates loss of visual function in dystrophic rats.
Royal College of Surgeons rats are genetically predisposed to undergo significant visual loss caused by a primary dysfunction of retinal pigment epithelial (RPE) cells. By using this model, we have examined the efficacy of subretinal transplantation of two independent human RPE cell lines each exhibiting genetic modifications that confer long-term stability in vitro. The two cell lines, a spontaneously derived cell line (ARPE19) and an extensively characterized genetically engineered human RPE cell line (h1RPE7), which expresses SV40 large T (tumor) antigen, were evaluated separately. Both lines result in a significant preservation of visual function as assessed by either behavioral or physiological techniques. This attenuation of visual loss correlates with photoreceptor survival and the presence of donor cells in the areas of rescued photoreceptors at 5 months postgrafting (6 months of age). These results demonstrate the potential of genetically modified human RPE cells for ultimate application in therapeutic transplantation strategies for retinal degenerative diseases caused by RPE dysfunction.
Lund
R D
RD
Department of Pathology, Institute of Ophthalmology, University College London, United Kingdom.
Adamson
P
P
Sauvé
Y
Y
Keegan
D J
DJ
Girman
S V
SV
Wang
S
S
Winton
H
H
Kanuga
N
N
Kwan
A S
AS
Beauchène
L
L
Zerbib
A
A
Hetherington
L
L
Couraud
P O
PO
Coffey
P
P
Greenwood
J
J
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D002461:Cell Line, Transformed / Q000637:transplantation; D002470:Cell Survival; D002472:Cell Transformation, Viral; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology*; D019416:Head Movements / Q000502:physiology; D006801:Humans; D010587:Phagocytosis; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000637:transplantation*; D011518:Proto-Oncogene Proteins; D051381:Rats; D011922:Rats, Mutant Strains; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D012374:Rod Cell Outer Segment / Q000378:metabolism / Q000473:pathology; D012684:Sensory Thresholds; D013539:Simian virus 40 / Q000235:genetics; D013477:Superior Colliculi / Q000503:physiopathology; D014183:Transplantation, Heterologous; D014787:Vision Tests; D014794:Visual Fields; D014796:Visual Perception; D000076202:c-Mer Tyrosine Kinase
D000952:Antigens, Polyomavirus Transforming; D005136:Eye Proteins; D011518:Proto-Oncogene Proteins; C097072:MERTK protein, human; C490765:Mertk protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase