論文 - 詳細
| RRC ID | 44701 |
|---|---|
| 著者 | Maeda T, Lee MJ, Palczewska G, Marsili S, Tesar PJ, Palczewski K, Takahashi M, Maeda A. |
| タイトル | Retinal pigmented epithelial cells obtained from human induced pluripotent stem cells possess functional visual cycle enzymes in vitro and in vivo. |
| ジャーナル | J Biol Chem |
| Abstract |
Differentiated retinal pigmented epithelial (RPE) cells have been obtained from human induced pluripotent stem (hiPS) cells. However, the visual (retinoid) cycle in hiPS-RPE cells has not been adequately examined. Here we determined the expression of functional visual cycle enzymes in hiPS-RPE cells compared with that of isolated wild-type mouse primary RPE (mpRPE) cells in vitro and in vivo. hiPS-RPE cells appeared morphologically similar to mpRPE cells. Notably, expression of certain visual cycle proteins was maintained during cell culture of hiPS-RPE cells, whereas expression of these same molecules rapidly decreased in mpRPE cells. Production of the visual chromophore, 11-cis-retinal, and retinosome formation also were documented in hiPS-RPE cells in vitro. When mpRPE cells with luciferase activity were transplanted into the subretinal space of mice, bioluminance intensity was preserved for >3 months. Additionally, transplantation of mpRPE into blind Lrat(-/-) and Rpe65(-/-) mice resulted in the recovery of visual function, including increased electrographic signaling and endogenous 11-cis-retinal production. Finally, when hiPS-RPE cells were transplanted into the subretinal space of Lrat(-/-) and Rpe65(-/-) mice, their vision improved as well. Moreover, histological analyses of these eyes displayed replacement of dysfunctional RPE cells by hiPS-RPE cells. Together, our results show that hiPS-RPE cells can exhibit a functional visual cycle in vitro and in vivo. These cells could provide potential treatment options for certain blinding retinal degenerative diseases. |
| 巻・号 | 288(48) |
| ページ | 34484-93 |
| 公開日 | 2013-11-29 |
| DOI | 10.1074/jbc.M113.518571 |
| PII | S0021-9258(20)55445-8 |
| PMID | 24129572 |
| PMC | PMC3843063 |
| MeSH | Animals Cell Differentiation Cells, Cultured Gene Expression Regulation, Enzymologic Humans Induced Pluripotent Stem Cells / cytology Induced Pluripotent Stem Cells / enzymology Induced Pluripotent Stem Cells / transplantation* Mice Retinal Degeneration / genetics* Retinal Degeneration / pathology Retinal Degeneration / therapy* Retinal Pigment Epithelium / enzymology Retinal Pigment Epithelium / transplantation* Retinaldehyde / biosynthesis Retinaldehyde / genetics Vision, Ocular / genetics Vision, Ocular / physiology cis-trans-Isomerases / deficiency cis-trans-Isomerases / genetics* |
| IF | 4.238 |
| 引用数 | 51 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | HiPS-RIKEN-1A(HPS0003) |