Long-term neuroretinal full-thickness transplants in a large animal model of severe retinitis pigmentosa.
BACKGROUND
The purpose of this study was to explore neuroretinal transplantation in a large animal model of severe retinitis pigmentosa and to establish graft development, long-term survival, graft-host integration, and effects on the host retina.


METHODS
Rhodopsin transgenic pigs, aged 6 months, received in one eye a fetal full-thickness neuroretinal sheet in the subretinal space by means of vitrectomy and retinotomy. Six months postoperatively, eyes were studied in the light microscope and with immunohistochemical markers. Full-field electroretinography (ERG) was performed at 4 and 6 months.


RESULTS
Laminated grafts with well-organized photoreceptors, rod bipolar cells, and Müller cells were found in five of six eyes. Neuronal connections between graft and host retina were not seen. In the five eyes containing a graft, the number of surviving rods in the host retina was significantly higher compared with unoperated eyes. The ERG did not reveal any significant difference in b-wave amplitude between operated and control eyes, but the cone-derived response in operated eyes increased significantly from 4 to 6 months while the rod response in control eyes decreased significantly.


CONCLUSIONS
Fetal full-thickness neuroretina can be transplanted safely to an eye with severe retinal degeneration. In their major part, the transplants develop a normal laminated morphology and survive for at least 6 months. Graft and host retinal neurons do not form connections. Retinal function in the host is reduced initially by the surgical trauma, but the presence of a well-laminated graft counteracts this effect and rescues rods from degeneration.
Ghosh
Fredrik
F
Department of Ophthalmology, BMC, Lund University Hospital, 22184, Lund, Sweden. fredrik.ghosh@med.lu.se
Engelsberg
Karl
K
English
Robert V
RV
Petters
Robert M
RM
D000818:Animals; D030801:Animals, Genetically Modified; D015415:Biomarkers; D003623:Dark Adaptation; D004195:Disease Models, Animal; D004596:Electroretinography; D005260:Female; D016332:Fetal Tissue Transplantation; D019084:Fluorescent Antibody Technique, Indirect; D005500:Follow-Up Studies; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006085:Graft Survival / Q000502:physiology; D009457:Neuroglia / Q000502:physiology; D011247:Pregnancy; D011493:Protein Kinase C / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000503:physiopathology / Q000637:transplantation*; D051245:Retinal Bipolar Cells / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology; D012174:Retinitis Pigmentosa / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism; D013552:Swine; D015293:Transducin / Q000378:metabolism; D014184:Transplantation, Homologous; D014821:Vitrectomy
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D012243:Rhodopsin; D011493:Protein Kinase C; D015293:Transducin