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Bile acid receptor signaling in retinopathy of prematurity

Award Number: R01EY034568
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2027

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Bile acid receptor signaling in retinopathy of prematurity - The proposed studies are relevant to the treatment of retinopathy of prematurity (ROP), the leading cause of preventable blindness in children. An important trigger for ROP development is the exposure of premature infants to oxygen after birth. This delays normal retinal vascular growth, still taking place in the premature retina. When the infant is brought back to room air, this leads to tissue ischemia, abnormal retinal neovascularization, and, possibly, retinal detachment and blindness. Available interventions are applied in the most advanced stages of the disease and consist of ablation of retinal neovascular tufts or intravitreal injections of anti-angiogenic factors (i.e., VEGF). All these procedures and treatments are associated with severe side effects, including significant loss of visual field and late recurrences. We have recently found that agonists of the nuclear receptor farnesoid-X-receptor (FXR) exert protective effects in an experimental model of ROP (oxygen-induced retinopathy; OIR). Interestingly, we have also found that FXR expression and levels of FXR endogenous ligands are downregulated in OIR, further supporting the hypothesis that leveraging/restoring FXR-dependent signaling could exert key protective effects in ROP/OIR. To confirm this, we found that FXR is present in retinal astrocytes and endothelial cells that are primarily affected in OIR. FXR stimulation may elicit anti-apoptotic responses in astrocytes and anti-angiogenic effects in retinal endothelial cells, thus targeting two key events involved in the induction and progression of OIR. Our working hypothesis is that alterations in retinal FXR signaling play a key role in ROP pathogenesis and the pharmacological modulation of these pathways represents a new therapeutic tool in limiting ROP pathology. We have designed experiments to be conducted in vivo, using the OIR model and in vitro experimental settings to 1) investigate the effects of modulating FXR receptor signaling in OIR; 2) investigate FXR signaling in retinal astrocytes and endothelial cells in OIR. The potential outcomes of the proposed studies could fill the need for new and better therapies for ROP.


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: 2025 ( Subtotal = $385,000 )
2025	2025	MEHARRY MEDICAL COLLEGE	1005 DR DB TODD JR BLVD	NASHVILLE	TN	37208	DAVIDSON	USA	Vision Research	004	4	6/11/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$187,204
2025	2025	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Vision Research	000	3	11/21/2024	NON-COMPETING CONTINUATION	$385,000
2025	2025	MEHARRY MEDICAL COLLEGE	1005 DR DB TODD JR BLVD	NASHVILLE	TN	37208	DAVIDSON	USA	Vision Research	002	4	4/9/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$385,000
2025	2025	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Vision Research	001	3	4/9/2025	NON-COMPETING CONTINUATION	-$385,000
2025	2024	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Vision Research	003	2	6/11/2025	NON-COMPETING CONTINUATION	-$187,204
														Subtotal = $385,000

Issue Date FY: 2024 ( Subtotal = $385,000 )
2024	2024	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Vision Research	000	2	11/30/2023	NON-COMPETING CONTINUATION	$385,000
														Subtotal = $385,000

Issue Date FY: 2023 ( Subtotal = $385,000 )
2023	2023	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Vision Research	000	1	1/11/2023	NEW	$385,000
														Subtotal = $385,000

Grand Total All Awards = $1,155,000

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Bile acid receptor signaling in retinopathy of prematurity

Award Number: R01EY034568

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2027

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