N-cadherin suppression enhances inner limiting membrane permeability for intravitreal cellular transplantation

Author:

Pelaez Daniel1ORCID,Gallo Ryan1ORCID,Dvoriantchikova Galina1,Moeyersoms Acadia1,Wang Hua1,Moulin Chloe1ORCID,Torres Zenith Acosta1,Lang Steven1ORCID,Ivanov Dmitry1

Affiliation:

1. University of Miami

Abstract

Abstract The efficient migration, survival, and engraftment of transplanted cells are important initial steps toward effective cellular therapies for retinal degenerative diseases. The inner limiting membrane (ILM), which separates the retina from the vitreous cavity, is a major barrier for intravitreally transplanted cells. Focusing on the cellular components of the ILM, we found that the cell adhesion molecule N-cadherin (NCAD) at Müller glia (MG) endfeet helps maintain this barrier. To increase ILM cellular permeability, we modulated NCAD expression via two approaches: an inducible MG-specific knockout animal model and with intravitreal self-deliverable siRNA injections. We show that NCAD suppression enhances retinal migration of multiple cell types after intravitreal transplantation, including mouse MG, human induced pluripotent stem cell-derived retinal ganglion cells, and human dental pulp stem cells. Our study may contribute to the development of targeted approaches for recipient tissue modulation to improve cellular therapies for retinal disease.

Publisher

Research Square Platform LLC

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