Role of choroid endothelial cells in the homeostasis of the outer retina

Abstract

Presentation Description : Beyond their role as blood conduits, endothelial cells (ECs) are organ-specific and secrete key angiocrine factors essential for organ differentiation and regeneration. We hypothesized that choroid ECs may regulate the maturation and homeostasis of the outer retina, and that functional defects of choroid ECs could be highly significant for the etiology and pathogenesis of age-related macular degeneration (AMD). We carried out a series of RNAseq analyses to study the changes in gene expression of mouse choroid ECs during retinal terminal differentiation, and to compare the transcriptome of ECs from adult choroid and other tissues. These studies, along with in vitro co-culture assays, the use of reporter mouse models and the generation of EC-specific knockout mice, support the notion that factors secreted by choroid ECs regulate retinal pigment epithelium (RPE) barrier function and the maintenance of adult choroid homeostasis and visual function in response to injury. We also identified a signaling loop involving the Hedgehog pathway between choroid ECs and a population of mesenchymal stem cell (MSC)-like choroidal perivascular cells, recently discovered in our laboratory. Crosstalk between RPE, choroid ECs and MSC-like cells may be key for such processes, and its disruption may contribute to the onset and pathogenesis of AMD.
Ignacio Benedicto^1*, Guillermo L. Lehmann^1*, Michael Ginsberg², Daniel J. Nolan², Rohan Bareja³, Olivier Elemento³, Nazia M. Alam^3,4, Glen T. Prusky^3,4, Pierre Llanos⁵, Sina Y. Rabbany⁵, Arvydas Maminishkis⁶, Sheldon S. Miller⁶, Alexandre Wojcinski⁷, Alexandra L. Joyner⁷, Shahin Rafii^2,8,9, Enrique Rodriguez-Boulan¹
*, equal contribution
1. Margaret Dyson Vision Research Institute, Department of Ophthalmology, Weill Cornell Medical College, New York, NY, USA; 2. Angiocrine Bioscience, Inc.; 3. Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY, USA; 4. Burke Medical Research Institute, White Plains, NY, USA; 5. Bioengineering Program, Hofstra University, Hempstead, NY, USA; 6. Section of Epithelial and Retinal Physiology and Disease, National Eye Institute, National Institutes of Health, Bethesda, MD, USA; 7. Memorial Sloan Kettering Cancer Center, New York, NY, USA; 8. Genetic Medicine, Weill Cornell Medical College, New York, NY, USA; 9. Ansary Stem Cell Institute, Weill Cornell Medical College, New York, NY, USA.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.