Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Metabolic basis of retinopathy of prematurity and potential treatment with anaplerotic substrates

Award Number: R01EY035701
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2025
PERIOD OF PERFORMANCE END DATE: 03/31/2030

Group Awards By:

View Award Description

Metabolic basis of retinopathy of prematurity and potential treatment with anaplerotic substrates - Project summary/abstract Supplemental oxygen is provided to premature infants to prevent mortality. Hyperoxia prevents mortality, however, hyperoxic exposure of premature infants inhibits retinal neurovascular development and causes retinopathy of prematurity (ROP). Findings from our work and other groups indicate that ROP development involves deficits in liver metabolism. For example, DHA, AA are produced in the liver, and these have been associated with the ROP. In addition, we have demonstrated that the liver-based HIF1-α is required to produce the retinal serine/one-carbon metabolites to prevent oxygen-induced retinopathy (OIR). Infants with low weight at birth are more prone to ROP, implying that nutrition plays a role in ROP development. In addition, premature infant mothers have different fat compositions in their milk. There are higher amounts of medium- chain fatty acids (MCFAs) and long-chain polyunsaturated fatty acids (LCPUFAs) in the milk of mothers of premature infants. Although LCPUFAs have been studied, both in the OIR model and in ROP clinical trials, the role of energy-generating MCFAs remains unknown. Our recent publication highlights that hyperoxia downregulates the entry of glycolytic carbon into the tricarboxylic acid cycle (TCA cycle) and upregulates glutamine-fueled anaplerosis in the Müller cells in response to hyperoxia. This lowers the amount of glutamine available for endothelial cell proliferation. We hypothesize, providing a substrate that can feed into TCA, can prevent glutamine diversion into TCA cycle. One of the top alternative substrates in the early stages of development is MCFA from maternal nutrition. We compared the fatty acid β-oxidation genes in the retina. We found statistically significantly higher expression of only MCFA utilization and ketone body utilization enzymes in OIR-resistant mouse strain. Our preliminary data shows a higher availability of MCFA octanoate in the blood of OIR-resistant strain. In addition, our liver RNAseq data indicates higher conversion of MCFA-CoAs into free fatty acid MCFAs and ketone bodies. We tested the utilization of medium-chain fatty acid-octanoate in the retinal explant experiments and found increased utilization in response to hyperoxia. Altogether, our data indicate that a balance between fatty acid utilization and nitrogen compound-based anaplerosis may be the underlying cause of oxygen-induced retinopathy development. The Aim of this grant is to study fatty acid metabolic exchanges between liver and retina at systems levels, and to use anaplerotic substrates in conjunction with Adeno-associated viruses (AAVs) based genetic manipulations of the fatty acid metabolic genes, to prevent oxygen-induced retinopathy.


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 = $462,072 )
2025	2025	TUFTS MEDICAL CENTER PARENT, INC.	800 WASHINGTON ST	BOSTON	MA	02111	SUFFOLK	USA	Vision Research	000	1	3/13/2025	NEW	$462,072
														Subtotal = $462,072

Grand Total All Awards = $462,072

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Metabolic basis of retinopathy of prematurity and potential treatment with anaplerotic substrates

Award Number: R01EY035701

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2025

PERIOD OF PERFORMANCE END DATE: 03/31/2030

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer