June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Transplantation strategy of human retinal ganglion cells for glaucoma
Author Affiliations & Notes
  • Tasneem Putliwala Sharma
    Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States
    Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Kathleen Ho
    Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Nicole Bodi
    Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Shahna Shahul Hameed
    Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Footnotes
    Commercial Relationships   Tasneem Sharma U.S. Patent Application No. 16/395,610, Code P (Patent); Kathleen Ho None; Nicole Bodi None; Shahna Shahul Hameed None
  • Footnotes
    Support  Unrestricted grant from Research to Prevent Blindness, Inc. to the Indiana University School of Medicine Department of Ophthalmology, Indiana CTSI Project Development Team Program (Grant # UL1TR002529), EyeFind Research Grant
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 3846. doi:
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    • Get Citation

      Tasneem Putliwala Sharma, Kathleen Ho, Nicole Bodi, Shahna Shahul Hameed; Transplantation strategy of human retinal ganglion cells for glaucoma. Invest. Ophthalmol. Vis. Sci. 2023;64(8):3846.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Glaucoma is a group of optic neuropathies characterized by retinal ganglion cell (RGC) death and visual field loss. Preventing neurodegenerative failure in glaucoma through stem cell technologies and preclinical human models for testing therapeutics and recapitulating human disease is an important step forward for translational research. Human induced pluripotent stem cell (iPSC) technology allows iPSC-RGCs to be generated in-vitro from commercial iPSCs and reprogrammed corneal fibroblasts. Validating a transplantation strategy of iPSC-RGCs in a human ocular model system would provide a translational approach for future glaucoma clinical trials. We aim to use our ocular translaminar autonomous system (TAS) perfusion model system to apply iPSC-RGC replacement to restore functional capacity in the degenerated human adult retina. This will allow us to analyze a potential therapeutic for late-stage disease when most RGCs are lost.

Methods : Human donor eyes were obtained from eye banks according to Declaration of Helsinki. De novo human iPSC-RGCs transfected with AAV2-GFP were seeded into human posterior cups. These eye cups were then cultured in the TAS model for 7 days under glaucomatous intraocular and intracranial pressure conditions (30 and 12 mmHg respectively) to generate a translaminar pressure gradient. We assessed survival of native donor RGCs with and without human iPSC-RGC transplantation through expression of cell survival, apoptosis, inflammatory and fibrotic markers by qRT-PCR, western blotting, and immunohistochemistry. Retinal function was measured through electroretinogram analysis.

Results : We successfully transplanted hiPSC-RGCs in posterior eye cups and maintained them in the TAS model for 7 days. In contrast to non-transplanted human donor eyes, the eyes transplanted with human iPSC-RGCs secreted soluble factors that increased survival of native donor RGCs. Additionally, we identified down-regulated gene expression of apoptosis, inflammation, and gliotic markers (BAX, CASP3, TLR4, IBA-1 and GFAP), decreased fibrotic expression (FN and COLIV) and increased retinal function in the transplanted retinas.

Conclusions : Our study identified that transplanted human iPSC-RGC promoted RGC survival under pressurized conditions. This suggests that human iPSC-RGCs could be utilized as a potential therapy to save retinal neurons and prevent neurodegeneration in glaucoma patients.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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