Tuesday, December 9, 2025 12/9/2025

Induced pluripotent stem cell approach to optic nerve regeneration

Award Number: R01EY022051
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2012
PERIOD OF PERFORMANCE END DATE: 05/31/2025

Group Awards By:

View Award Description

Induced pluripotent stem cell approach to optic nerve regeneration - ABSTRACT Glaucoma is the most prevalent optic neuropathy where a progressive degeneration of retinal ganglion cells (RGCs) leads to vision loss. Our long-term goal is to help prevent the degeneration of glaucomatous RGCs by characterizing pluripotent stem cells as a renewable source of RGCs for autologous ex vivo cell therapy. The objective of this renewal application is to address the next question relevant to the potential clinical application of human pluripotent cell-derived RGCs: whether or not these cells can elaborate guidable axons that can navigate out of the host retina and seek bonafide targets, essential for reversing vision loss. To our knowledge this question, essential for practical ex-vivo stem cell approach to glaucomatous degeneration, remains unanswered. The central hypothesis of the proposed study is that human induced pluripotent stem cells derived RGCs (hiPSC-RGCs) elaborate guidable axons, regulated by the mTOR pathway, an intrinsic regulator axonogenesis and regeneration. Our reasoning is based on our observations that hiPSC-RGCs are (1) stable, functional, and safe (2) express guidance receptors and respond to both proximal (intra- retinal) and distal (extra-retinal) guidance cues, and (3) have active mTOR pathway, regulating development and neuritogenesis. Our rationale is that the ability of hiPSC-RGCs to recapitulate the mechanism of axon growth and guidance will posit them as a viable reagent to functionally replace degenerated RGCs in glaucoma. The following specific aims are proposed to test the hypothesis: Aim 1: To determine the competence of hiPSC-RGCs for axon guidance and target specificity, Aim 2: To determine the competence of hiPSC-RGCs for mTOR-dependent axonogenesis and regeneration in vitro, and Aim 3: To determine mTOR-dependent hiPSC-RGC axonogenesis in neonatal and adult retina. The potential of hiPSC-RGCs for axonogenesis and axon guidance will be examined in co-culture paradigm using the microfluidic system in controlled conditions. Immunocytochemical analysis of known pathways and transcriptional profiling would identify candidate regulatory factors. The regenerative ability of hiPSC-RGCs in the context of mTOR pathway will be examined in a microfluidic model of the axotomy model, established in our lab. Transcription profile at pre-axotomy, axotomy, and post-axotomy stages would identify regenerative gene regulatory network. Finally, regenerative capacity of hiPSC-RGCs and the influence of the mTOR pathway will be examined in vivo in neonatal retina, where environment is conducive for axon growth and in a degenerative adult environment in animal model of glaucoma. Our research proposal is innovative because it will determine whether the de novo generated neurons can functionally replace those that make long distance connections such as RGCs and bridge a gap in our knowledge about human RGC development and axon path finding, a barrier to optic nerve regeneration. The emerging information will be significant because it will not only address each of the most significant barriers that currently make the ex-vivo stem cell therapy approach impractical but also lead to the development of a robust model system for testing normal/pathological mechanisms of RGC development and for screening drugs and genes for additional new therapeutic approaches for glaucomatous retinal degeneration.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2022	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	4215 EMILE ST	OMAHA	NE	68105	DOUGLAS	USA	Vision Research	000	9	11/24/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Vision Research	000	9	5/15/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $369,813 )
2022	2022	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Vision Research	000	9	7/5/2022	NON-COMPETING CONTINUATION	$369,813
														Subtotal = $369,813

Issue Date FY: 2021 ( Subtotal = $369,812 )
2021	2021	BOARD OF REGENTS OF THE UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Vision Research	000	8	5/26/2021	NON-COMPETING CONTINUATION	$369,812
														Subtotal = $369,812

Issue Date FY: 2020 ( Subtotal = $381,250 )
2020	2020	UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Vision Research	000	7	5/21/2020	NON-COMPETING CONTINUATION	$381,250
														Subtotal = $381,250

Issue Date FY: 2019 ( Subtotal = $381,250 )
2019	2019	UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Vision Research	000	6	5/24/2019	NON-COMPETING CONTINUATION	$381,250
														Subtotal = $381,250

Issue Date FY: 2018 ( Subtotal = $380,211 )
2018	2018	UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Vision Research	001	5	5/17/2018	COMPETING CONTINUATION	$381,042
2018	2016	UNIVERSITY OF NEBRASKA	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Vision Research	000	4	2/12/2018	EXTENSION WITH OR WITHOUT FUNDS	-$831
														Subtotal = $380,211

Issue Date FY: 2016 ( Subtotal = $371,250 )
2016	2016	UNIVERSITY OF NEBRASKA MEDICAL CENTER	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Vision Research	001	4	1/29/2016	EXTENSION WITH OR WITHOUT FUNDS	$37,125
2016	2016	UNIVERSITY OF NEBRASKA MEDICAL CENTER	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Vision Research	000	4	11/13/2015	EXTENSION WITH OR WITHOUT FUNDS	$334,125
														Subtotal = $371,250

Issue Date FY: 2015 ( Subtotal = $363,825 )
2015	2015	UNIVERSITY OF NEBRASKA MEDICAL CENTER	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Vision Research	001	3	1/30/2015	NON-COMPETING CONTINUATION	$29,700
2015	2015	UNIVERSITY OF NEBRASKA MEDICAL CENTER	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Vision Research	000	3	11/20/2014	NON-COMPETING CONTINUATION	$334,125
														Subtotal = $363,825

Issue Date FY: 2014 ( Subtotal = $363,825 )
2014	2014	UNIVERSITY OF NEBRASKA MEDICAL CENTER	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Vision Research	000	2	11/21/2013	NON-COMPETING CONTINUATION	$334,125
2014	2014	UNIVERSITY OF NEBRASKA MEDICAL CENTER	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Vision Research	001	2	2/26/2014	NON-COMPETING CONTINUATION	$29,700
														Subtotal = $363,825

Issue Date FY: 2013 ( Subtotal = $371,250 )
2013	2013	UNIVERSITY OF NEBRASKA MEDICAL CENTER	987835 NEBRASKA MEDICAL CENTER	OMAHA	NE	68198	DOUGLAS	USA	Vision Research	000	1	11/19/2012	NEW	$371,250
														Subtotal = $371,250

Grand Total All Awards = $3,352,486

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Induced pluripotent stem cell approach to optic nerve regeneration

Award Number: R01EY022051

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/01/2012

PERIOD OF PERFORMANCE END DATE: 05/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer