Report on the National Eye Institute Audacious Goals Initiative: Replacement of Retinal Ganglion Cells from Endogenous Cell Sources.

Monica L Vetter,Peter F Hitchcock

doi:10.1167/tvst.6.2.5

Abstract

This report emerges from a workshop convened by the National Eye Institute (NEI) as part of the “Audacious Goals Initiative” (AGI). The workshop addressed the replacement of retinal ganglion cells (RGCs) from exogenous and endogenous sources, and sought to identify the gaps in our knowledge and barriers to progress in devising cellular replacement therapies for diseases where RGCs die. Here, we briefly review relevant literature regarding common diseases associated with RGC death, the genesis of RGCs in vivo, strategies for generating transplantable RGCs in vitro, and potential endogenous cellular sources to regenerate these cells. These topics provided the clinical and scientific context for the discussion among the workshop participants and are relevant to efforts that may lead to therapeutic approaches for replacing RGCs. This report also summarizes the content of the workshop discussion, which focused on: (1) cell sources for RGC replacement and regeneration, (2) optimizing integration, survival, and synaptogenesis of new RGCs, and (3) approaches for assessing the outcomes of RGC replacement therapies. We conclude this report with a summary of recommendations, based on the workshop discussions, which may guide vision scientists seeking to develop therapies for replacing RGCs in humans.

Highlights

In developed countries, losing vision is among the most feared ailments, and across all countries blindness creates enormous economic and social burdens[1]
Exogenous Sources While the focus of the workshop was on endogenous sources for retinal ganglion cells (RGCs) replacement, the group first discussed recent advances made in using exogenous sources to generate RGCs
Either human embryonic stem cells (ESCs) or induced pluripotent stem cells were identified as a viable source for donor cells because they can be derived in unlimited numbers, and can be directed to generate retinal progenitor cells that under defined conditions differentiate into RGCs or other retinal cell types

Summary

Introduction

In developed countries, losing vision is among the most feared ailments, and across all countries blindness creates enormous economic and social burdens[1] (and references cited therein).

Results

Conclusion