Exploration of Retinal Ganglion Endogenous Repair after Injury using Engineered hPSCs
About This Grant
Abstract. In glaucoma and other optic neuropathies, retinal ganglion cell (RGC) axons become damaged, leading to cell death and permanent blindness. While some species, including fish, salamanders, and birds, exhibit a remarkable potential for regenerating lost neurons, mammals seem to have lost this capability. In species that can regenerate after injury, changes in early expressed transcription factors (TFs) convert a portion of pre- existing Müller glia (MG) into proliferative stem-like progenitors. Subsequently, cell-fate specifying TFs trigger cell cycle exit and retinal specification. Since precise knowledge of the TFs controlling development and regeneration is incomplete, there is a critical need for further investigation into how TFs enable Müller cells to respond to injury and how waves of TFs lead to proliferation and ultimately to RGC specification. Thus, our main objective is to use human pluripotent stem cell (PSC) -derived 3D retinal organoids (rORGs) as a model to explore endogenous glia-to-neuron repair in the retina. In AIM1a, we will isolate and study lineage-traced Müller glia from rORGs under quiescent conditions and after stimulation with TFs promoting proliferation (β- catenin, LIN28) and/or neurogenesis (ASCL1, NEUROG2). This will be done primarily by AAV-delivered TF overexpression. In AIM1b, additional targets will focus on recently described regeneration roadblocks (NFIA, -B, -X, and ATF7IP-JUNB-ZNF207[AJZ]) that converge around STAT signaling. CRISPR interference will suppress these targets, which we expect to enhance multipotent progenitor cell formation. In nature, injury appears to participate in regeneration, so in AIM2, we will use a cell type-specific drug-inducible Caspase9 (iCasp9) RGC cell ablation model to study the effects of cell injury on MG activation. This will make it much easier to observe the disappearance and re-appearance of ablated and regenerated lineage trace reporter RGCs. In addition, cell damage/death may induce the signaling pathways necessary for regeneration, and our approach will allow us to study that at different stages. In AIM3, we will pivot from enhancing MG-derived retinal progenitors to making actual RGCs. As with early TF-focused experiments, developmentally relevant TFs will be delivered by AAV to steer progenitors toward an RGC fate. Overall, we aim to identify pro- regenerative factors, with the primary goal of restoring the histological architecture of an intact functional retina, which will hopefully lead to new approaches for restoring vision for the millions of individuals who have optic neuropathy-related vision loss.
Grant Summary
Exploration of Retinal Ganglion Endogenous Repair after Injury using Engineered hPSCs is a NEI - National Eye Institute grant providing up to $702K for university, nonprofit, healthcare org. Applications are due 2030-04-30 (open). Check eligibility and apply with FindGrants.
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Up to $702K
2030-04-30
- 1Confirm your organization is eligible for Exploration of Retinal Ganglion Endogenous Repair after Injury using Engineered hPSCs from NEI - National Eye Institute, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
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Exploration of Retinal Ganglion Endogenous Repair after Injury using Engineered hPSCs: Frequently Asked Questions
Who is eligible for the Exploration of Retinal Ganglion Endogenous Repair after Injury using Engineered hPSCs?
Exploration of Retinal Ganglion Endogenous Repair after Injury using Engineered hPSCs is offered by NEI - National Eye Institute and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Exploration of Retinal Ganglion Endogenous Repair after Injury using Engineered hPSCs provide?
Exploration of Retinal Ganglion Endogenous Repair after Injury using Engineered hPSCs provides up to $702K per award from NEI - National Eye Institute. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Exploration of Retinal Ganglion Endogenous Repair after Injury using Engineered hPSCs deadline?
Applications for Exploration of Retinal Ganglion Endogenous Repair after Injury using Engineered hPSCs are due 2030-04-30 (open). Because deadlines can change, verify the date with the funder, NEI - National Eye Institute, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Exploration of Retinal Ganglion Endogenous Repair after Injury using Engineered hPSCs?
To apply for Exploration of Retinal Ganglion Endogenous Repair after Injury using Engineered hPSCs, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NEI - National Eye Institute.