Article
Survival of subretinally implanted human fetal and adult retinal pigment epithelium monolayers on cell carriers in rabbits
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Published: | May 30, 2012 |
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Outline
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A large-eye animal model was developed with chinchilla-bastard rabbits for cost-efficient tissue engineering studies of retinal pigment epithelial (RPE) replacement on healthy tissue.
Fetal & adult human RPE cultures were grown for at least 6 weeks on biostable polyester membranes (PET); epithelial polarity was verified with transepithelial resistance above 250 Ω cm2. Bullet-shaped implants were made with a trephine.
Vitrectomy was performed in 2–2.5 kg rabbits and a small retinal detachment (RD) created. The implant was then passed through an enlarged opening of the retina with a custom-made shooter instrument. The RD over acellular implants resolved within 4–7 days, but resulted in an outer retinal atrophy without inflammation. RD alone without implant placement induced neither retinal atrophy nor inflammation.
Subretinal implantation of fetal hRPE on PET in non-immunosuppressed rabbits (n>30) resulted after 4 days in neural retinal edema above the RPE implant on SD-OCT and funduscopy. After 1 week, an atrophy of the retina overlying the fetal xeno-transplant was observed, remaining stable thereafter. Histology obtained 4 weeks after implantation showed an almost continuous xeno-RPE monolayer on PET. These findings were largely similar in 5 consecutive rabbits with adult hRPE cells. These data demonstrate successful subretinal delivery of cultured RPE on PET carriers. The xeno-RPE seems to survive over 4 weeks and may actively evade destruction through its immune privilege.