Single-cell profiling reveals an endothelium-mediated immunomodulatory pathway in the eye choroid

Guillermo L. Lehmann, Christin Hanke-Gogokhia, Yang Hu, Rohan Bareja, Zelda Salfati, Michael Ginsberg, Daniel J. Nolan, Santiago P. Mendez-Huergo, Tomas Dalotto-Moreno, Alexandre Wojcinski, Francisca Ochoa, Shemin Zeng, Juan P. Cerliani, Lampros Panagis, Patrick J. Zager, Robert F. Mullins, Shuntaro Ogura, Gerard A. Lutty, Jakyung Bang, Jonathan H. ZippinCarmelo Romano, Gabriel A. Rabinovich, Olivier Elemento, Alexandra L. Joyner, Shahin Rafii, Enrique Rodriguez-Boulan, Ignacio Benedicto

Research output: Contribution to journalArticlepeer-review

Abstract

The activity and survival of retinal photoreceptors depend on support functions performed by the retinal pigment epithelium (RPE) and on oxygen and nutrients delivered by blood vessels in the underlying choroid. By combining single-cell and bulk RNA sequencing, we categorized mouse RPE/choroid cell types and characterized the tissue-specific transcriptomic features of choroidal endothelial cells. We found that choroidal endothelium adjacent to the RPE expresses high levels of Indian Hedgehog and identified its downstream target as stromal GLI1+ mesenchymal stem cell-like cells. In vivo genetic impairment of Hedgehog signaling induced significant loss of choroidal mast cells, as well as an altered inflammatory response and exacerbated visual function defects after retinal damage. Our studies reveal the cellular and molecular landscape of adult RPE/choroid and uncover a Hedgehog-regulated choroidal immunomodulatory signaling circuit. These results open new avenues for the study and treatment of retinal vascular diseases and choroid-related inflammatory blinding disorders.

Original languageEnglish (US)
Article numbere20190730
JournalJournal of Experimental Medicine
Volume217
Issue number6
DOIs
StatePublished - Jun 1 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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