Pathological elucidation in induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelial Cells established from Patient with Retinitis Pigmentosa Carrying novel gene abnormality
| Project/Area Number |
18K16923
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56060:Ophthalmology-related
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| Research Institution | Kyoto University |
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Principal Investigator |
Iwai Sachiko 京都大学, 医学研究科, 特定研究員 (00768905)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | MERTK / 網膜色素変性 / 疾患特異的iPS細胞 / iPS-RPE / MERTK遺伝子変異 / 網膜色素変性症 / 遺伝子変異 |
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| Outline of Final Research Achievements |
Retinitis pigmentosa (RP) is an incurable retinal degenerative disease with a yet unelucidated mechanism of disease progression. Mer tyrosine kinase (MERTK) is one of the causal genes of RP. MERTK is reportedly expressed in retinal pigment epithelium (RPE); it is essential for phagocytosis of the photoreceptor outer segment. Here, we established induced pluripotent stem cells (iPSC) from an RP patient with compound heterozygous mutations in MERTK and from healthy subjects; the RP patient- and healthy control-derived iPSCs were differentiated into RPE cells. There were no morphological differences between the diseased and normal RPE cells. However, the internalization of latex beads or photoreceptor outer segments in diseased iPSC-RPE cells was significantly deteriorated compared to normal iPSC-RPE cells.
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| Academic Significance and Societal Importance of the Research Achievements |
網膜色素変性症は遺伝性の網膜脈絡膜変性疾患で、100以上の原因遺伝子が同定されているが、患者から病変組織を採取することができず正確にヒトの病態を再現することが難しく、これまで詳細な病態解明や治療法の開発が困難であった。しかし、我々はiPS細胞からRPE（iPS-RPE）へ分化誘導する方法を確立し、患者由来iPS-RPEを得ることができるようになった。本研究では、新規MERTK遺伝子変異をもつ患者由来iPS-RPEの貪食機能が、健常者由来iPS-RPEと比較して低下していることが明らかになった。このin vitroの結果は、今後病態解明や将来的な治療法開発の礎を築くことに役立つ可能性がある。
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Report
(3 results)
Research Products
(2 results)
