February 6
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12:00 PM
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1:00 PM
Engineering the retinal microenvironment to improve donor neuron integration post-transplantation
Jonathan Soucy, PhD
Postdoctoral Research Fellow
Ophthalmology Department at Harvard Medical School
Schepens Eye Research Institute of Mass. Eye and Ear
Abstract:
Neuron transplantation is an exciting solution for replacing retinal ganglion cells (RGCs) lost in glaucoma and other optic neuropathies. However, one significant barrier to successful donor RGC integration is their migration into the ganglion cell layer (GCL). To address this, we developed an approach to control donor neurons in vivo by engineering their microenvironment post-transplantation.
Using an in silico analysis of the developing human retina and a functional in vitro assay, we evaluated receptor-ligand candidates for their potential to control RGC migration. Among these, SDF1 emerged as our lead molecule. By establishing an SDF1 gradient in vivo, we increased donor RGC integration into the GCL nearly threefold. While this strategy has not yet restored vision, only donor RGCs that migrated into the GCL extended neurites toward the optic nerve head and expressed mature RGC markers.
This work establishes a framework for controlling donor cell function through tissue microenvironment engineering, laying the foundation for future advancements in stem cell-based therapies for vision restoration.
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