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Investigation of the neuroimmune axis in retinal regeneration.

Award Number: R00EY033402
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2027

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Investigation of the neuroimmune axis in retinal regeneration. - Project Summary/Abstract Loss of vision has a devastating impact on an individual's quality of life. Most blinding diseases result from loss of neurons in the retina. A promising strategy to treat sight-threatening diseases, is to harness the regenerative potential of cells within the retina. Müller glia (MG), possess an extraordinary capacity in lower vertebrates to regenerate retinal neurons. However, in mammalian retinas, including humans, MG are unable to replace neurons lost to injury or disease. Recently, we have developed strategies to neurogenically reprogram MG in adult mice by overexpressing the transcription factor Ascl1 in MG. Remarkably, the treatment of Ascl1 overexpression, combined with NMDA-induced retinal damage and histone deacetylase (HDAC) inhibition, causes MG to regenerate functional neurons in the adult mammalian retina. While this is significant progress towards realizing the therapeutic potential of MG, only a subset of MG successfully reprogram into neurogenic progenitors while another subset of MG express genes associated with inflammatory processes. We hypothesized that the inflammation that accompanies neuronal cell loss restricts the regenerative potential of MG. Indeed, we recently found that ablation of microglia, the endogenous immune cell of the retina, dramatically improved MG-mediated retinal regeneration. This finding implicates the neuroimmune system as a key component of the regenerative response of the mammalian retina. However, little is known about the neuroimmune interface in retinal repair strategies such as endogenous regeneration. This proposal outlines studies to better understand the neuroimmune axis during MG-mediated retinal regeneration and to develop immunomodulation strategies to improve the regenerative capacity of the mammalian retina. The data generated in this proposal will be foundational to Dr. Todd's ultimate goal of becoming an independent investigator. During the K99 portion, Dr. Todd will expand his technical and theoretical expertise in neuroimmunology to accomplish his aims studying immune-glial interactions during retinal regeneration. New collaborations will be established with investigators in neuroimmunology and further training activities will prepare Dr. Todd to become a successful investigator in the field. The training portion of this proposal will take place at the University of Washington, which offers exceptional access to both research equipment and faculty expertise to assist in the accomplishment of the applicant's goals.


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 = $237,816 )
2026	2026	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Vision Research	000	5	2/6/2026	NON-COMPETING CONTINUATION	$237,816
														Subtotal = $237,816

Issue Date FY: 2025 ( Subtotal = $246,265 )
2025	2025	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Vision Research	000	4	3/17/2025	NON-COMPETING CONTINUATION	$246,265
														Subtotal = $246,265

Issue Date FY: 2024 ( Subtotal = $282,784 )
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Vision Research	000	3	1/29/2024	EXTENSION WITH OR WITHOUT FUNDS	$249,000
2024	2024	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Vision Research	001	3	5/15/2024	EXTENSION WITH OR WITHOUT FUNDS	$33,784
														Subtotal = $282,784

Grand Total All Awards = $766,865

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Investigation of the neuroimmune axis in retinal regeneration.

Award Number: R00EY033402

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2027

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