1. Role of the Internal Limiting Membrane in Structural Engraftment and Topographic Spacing of Transplanted Human Stem Cell-Derived Retinal Ganglion Cells.
- Author
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Zhang KY, Tuffy C, Mertz JL, Quillen S, Wechsler L, Quigley HA, Zack DJ, and Johnson TV
- Subjects
- Animals, Cell Membrane chemistry, Coculture Techniques, Extracellular Matrix metabolism, Humans, Mice, Mice, Inbred C57BL, Neurites metabolism, Peptide Hydrolases metabolism, Retina metabolism, Retina pathology, Retinal Ganglion Cells cytology, Retinal Ganglion Cells transplantation, Stem Cells cytology, Stem Cells metabolism, Cell Membrane metabolism, Retinal Ganglion Cells metabolism
- Abstract
Retinal ganglion cell (RGC) replacement holds potential for restoring vision lost to optic neuropathy. Transplanted RGCs must undergo neuroretinal integration to receive afferent visual signals for processing and efferent transmission. To date, retinal integration following RGC transplantation has been limited. We sought to overcome key barriers to transplanted human stem cell-derived RGC integration. Following co-culture ex vivo on organotypic mouse retinal explants, human RGCs cluster and extend bundled neurites that remain superficial to the neuroretina, hindering afferent synaptogenesis. To enhance integration, we increased the cellular permeability of the internal limiting membrane (ILM). Extracellular matrix digestion using proteolytic enzymes achieved ILM disruption while minimizing retinal toxicity and preserving glial reactivity. ILM disruption is associated with dispersion rather than clustering of co-cultured RGC bodies and neurites, and increased parenchymal neurite ingrowth. The ILM represents a significant obstacle to transplanted RGC connectivity and its circumvention may be necessary for functional RGC replacement., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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