期刊
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
卷 58, 期 2, 页码 -出版社
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.16-20738
关键词
preclinical model; embryonic stem cells; retinal pigment epithelium; photoreceptor; phosphate-buffered saline; sodium iodate; real-time imaging
资金
- Karolinska Institute
- Crown Princess Margareta's Foundation for the Visually Impaired
- Edwin Jordan Foundation for Ophthalmological Research
- Swedish Eye Foundation
- King Gustav V Foundation
- ARMEC Lindeberg Foundation
- Cronqvist Foundation
PURPOSE. Subretinal suspension transplants of human embryonic stem cell-derived retinal pigment epithelial cells (hESC-RPE) have the capacity to form functional monolayers in naive eyes. We explore hESC-RPE integration when transplanted in suspension to a large-eyed model of geographic atrophy (GA). METHODS. Derivation of hESC-RPE was performed in a xeno-free and defined manner. Subretinal bleb injection of PBS or sodium iodate (NaIO3) was used to induce a GA-like phenotype. Suspensions of hESC-RPE were transplanted to the subretinal space of naive or PBS-/NaIO3-treated rabbits using a transvitreal pars plana technique. Integration of hESC-RPE was monitored by multimodal real-time imaging and by immunohistochemistry. RESULTS. Subretinal blebs of PBS or NaIO3 caused different degrees of outer neuroretinal degeneration, RPE hyperautofluorescence, focal RPE loss, and choroidal atrophy; that is, hallmark characteristics of GA. In nonpretreated naive eyes, hESC-RPE integrated as subretinal monolayers with preserved overlying photoreceptors, yet not in areas with outer neuroretinal degeneration and native RPE loss. When transplanted to eyes with PBS-/NaIO3-induced degeneration, hESC-RPE failed to integrate. CONCLUSIONS. In a large-eyed preclinical model, subretinal suspension transplants of hESC-RPE did not integrate in areas with GA-like degeneration.
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