MERTK-Dependent Ensheathment of Photoreceptor Outer Segments by Human Pluripotent Stem Cell-Derived Retinal Pigment Epithelium

被引：24

作者：

Almedawar, Seba ^{[1
]}

Vafia, Katerina ^{[1
]}

Schreiter, Sven ^{[1
]}

Neumann, Katrin ^{[2
]}

Khattak, Shahryar ^{[2
]}

Kurth, Thomas ^{[2
]}

Ader, Marius ^{[1
]}

Karl, Mike O. ^{[1
,3
]}

Tsang, Stephen H. ^{[4
]}

Tanaka, Elly M. ^{[5
]}

机构：

[1] Tech Univ Dresden, CMCB, CRTD, Fetscherstr 105, D-01307 Dresden, Germany

[2] Tech Univ Dresden, CMCB, Technol Platform, Fetscherstr 105, D-01307 Dresden, Germany

[3] German Ctr Neurodegenerat Dis DZNE Dresden, Tatzberg 41, D-01307 Dresden, Germany

[4] CUMC, Edward S Harkness Eye Inst, 635 West 165th St, New York, NY 10032 USA

[5] Vienna Bioctr VBC, Res Inst Mol Pathol Imp, Campus Vienna Bioctr 1, A-1030 Vienna, Austria

来源：

STEM CELL REPORTS | 2020年 / 14卷 / 03期

关键词：

ALPHA-V-BETA-5; INTEGRIN; PHAGOCYTOSIS; ACTIVATION; DYSTROPHY; PROTEIN; KINASE; GAS6;

D O I：

10.1016/j.stemcr.2020.02.004

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Maintenance of a healthy photoreceptor-retinal pigment epithelium (RPE) interface is essential for vision. At the center of this interface, apical membrane protrusions stemming from the RPE ensheath photoreceptor outer segments (POS), and are possibly involved in the recycling of POS through phagocytosis. The molecules that regulate POS ensheathment and its relationship to phagocytosis remain to be deciphered. By means of ultrastructural analysis, we revealed that Mer receptor tyrosine kinase (MERTK) ligands, GAS6 and PROS1, rather than alpha V beta 5 integrin receptor ligands, triggered POS ensheathment by human embryonic stem cell (hESC)-derived RPE. Furthermore, we found that ensheathment is required for POS fragmentation before internalization. Consistently, POS ensheathment, fragmentation, and internalization were abolished in MERTK mutant RPE, and rescue of MERTK expression in retinitis pigmentosa (RP38) patient RPE counteracted these defects. Our results suggest that loss of ensheathment due to MERTK dysfunction might contribute to vision impairment in RP38 patients.

引用

页码：374 / 389

页数：16

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