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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

Abstract

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 αVβ5 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.

Details

OriginalspracheEnglisch
Seiten (von - bis)374-389
Seitenumfang16
FachzeitschriftStem cell reports
Jahrgang14
Ausgabenummer3
PublikationsstatusVeröffentlicht - 10 März 2020
Peer-Review-StatusJa

Externe IDs

PubMedCentral PMC7066375
Scopus 85081643637
ORCID /0000-0001-5624-1717/work/142239010
ORCID /0000-0002-0926-6556/work/142250475
ORCID /0000-0001-9467-7677/work/161888174

Schlagworte

Ziele für nachhaltige Entwicklung

Schlagwörter

  • Cell Line, Human Embryonic Stem Cells/metabolism, Humans, Ligands, Mutation/genetics, Phagocytosis, Pluripotent Stem Cells/metabolism, Receptors, Vitronectin/metabolism, Retinal Photoreceptor Cell Outer Segment/enzymology, Retinal Pigment Epithelium/metabolism, c-Mer Tyrosine Kinase/genetics

Bibliotheksschlagworte