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Fatty acid binding-proteins and endocannabinoids in the retina; roles in glial reactivity and reprogramming of Muller glia into progenitor cells

Award Number: R01EY032141
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary: There is a rapidly growing body of evidence that Müller glia can are a source of retinal progenitors to promote neural regeneration. Many studies have demonstrated that Müller glia can become proliferating progenitor cells in the retinas of different vertebrate species. Most reports have studied Müller glia-derived progenitors in acutely damaged retinas. However, little is known about the mechanisms that stimulate neurogenesis from Müller glia-derived progenitors in undamaged retinas or retinas undergoing slow, progressive degeneration. Furthermore, the regeneration of retinal neurons in warm-blooded vertebrates is limited compared to that seen in cold-blooded vertebrates. Therefore, the identification of the secreted factors and signaling pathways that block or stimulate neural regeneration from Müller glia-derived progenitors is crucially important to developing new therapies to treat degenerative diseases of the human retina. We have obtained compelling novel preliminary data indicating that Fatty acid-binding proteins (FABPs) and endocannabinoids impact the de-differentation and reprogramming of Müller glia into proliferating, neurogenic retinal progenitors in chicks and mice. We will investigate how the phenotype and plasticity of the Müller glia are regulated by FABPs and endocannabinoids in normal, damaged and growth factor-treated retinas. We will use a combination of pharmacological and genetic approaches to selectively activate or inhibit FABPs and endocannabinoid-signaling. We will compare and contrast how FABPs and endocannabinoid-signaling impacts the formation of Müller glia-derived progenitors in chick and rodent model systems with different inherent capacities for retinal regeneration. We expect that the completion of the experiments described in this proposal will provide significant new information regarding how mature Müller glia can be reprogrammed into Müller glia-derived progenitors that regenerate retinal neurons. Identification and understanding of the mechanisms that enhance the neurogenic potential of Müller glia is required to develop new therapies for sight- threatening diseases, such as glaucoma, retinitis pigmentosa and macular degeneration that involve the loss of retinal neurons.


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: 2024 ( Subtotal = $378,405 )
2024	2024	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Vision Research	000	4	12/8/2023	NON-COMPETING CONTINUATION	$378,405
														Subtotal = $378,405

Issue Date FY: 2023 ( Subtotal = $379,061 )
2023	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Vision Research	001	3	3/8/2023	NON-COMPETING CONTINUATION	$37,906
2023	2023	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Vision Research	000	3	12/1/2022	NON-COMPETING CONTINUATION	$341,155
														Subtotal = $379,061

Issue Date FY: 2022 ( Subtotal = $368,289 )
2022	2022	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Vision Research	000	2	12/29/2021	NON-COMPETING CONTINUATION	$341,712
2022	2022	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Vision Research	001	2	1/27/2022	NON-COMPETING CONTINUATION	$26,577
														Subtotal = $368,289

Issue Date FY: 2021 ( Subtotal = $376,624 )
2021	2021	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Vision Research	000	1	12/17/2020	NEW	$376,624
														Subtotal = $376,624

Grand Total All Awards = $1,502,379

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Fatty acid binding-proteins and endocannabinoids in the retina; roles in glial reactivity and reprogramming of Muller glia into progenitor cells

Award Number: R01EY032141

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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