254 - Effects of early antioxidants and/or fish oil supplementation on Notch ligands and receptors in a rat model of oxygen-induced retinopathy.

Friday, April 28, 2023

5:15 PM – 7:15 PM ET

Poster Number: 254
Publication Number: 254.13

Sidra Bashir, State University of New York Downstate Medical University, Brooklyn, NY, United States; Kay Beharry, SUNY Downstate Health Sciences University, Brooklyn, NY, United States; Jacob (Jack) v\V. Aranda, State University of New York Downstate Medical Center College of Medicine, Brooklyn, NY, United States

Presenting Author(s)

Sidra Bashir, MD (she/her/hers)

Neonatology Fellow
State University of New York Downstate Medical University
NYC, New York, United States

Background:

Notch ligands and receptors are important for cell specification and angiogenesis, but their role in oxygen-induced retinopathy is not well studied. The notch ligands, delta like ligand (DLL)-4 and Jagged-1 signaling to Notch receptors influence angiogenesis. DLL-4 inhibits VEGF receptor (VEGFR)-2 to curtail angiogenesis. Its deletion results in vascular abnormalities, enhanced angiogenic sprouting, and increased endothelial cell proliferation. On the other hand, Jagged-1 signaling promotes angiogenesis and is induced by hypoxia.

Objective:

We tested the hypothesis that early supplementation with antioxidants and/or fish oil induces DLL-4-Notch signaling and curtails Jagged-1 to prevent intermittent hypoxia (IH)-induced angiogenesis in a rat model for oxygen-induced retinopathy.

Design/Methods:

Newborn rats were exposed to brief IH episodes (12%) during hyperoxia (50% O₂) from the first day of life (P0) until P14 during which they received daily oral supplementation with: 1) fish oil; 2) coenzyme Q10 (CoQ10) in olive oil (OO); 3) glutathione nanoparticles (nGSH); 4) fish oil+CoQ10; or 5) OO (placebo controls). Pups were placed in room air (RA) from P14 to P21 with no further treatment. Control littermates remained in RA from birth to P21 with all treatments identical. Oxidative stress, apoptosis, ocular histopathology and levels of Notch-1, Notch-4, DLL-4 and Jagged-1were assessed in the serum, retina, and choroid at P21.

Results: Neonatal IH resulted in severe abnormalities in the retina and astrocyte template. This was associated with induced oxidative stress (evidenced by Malondialdehyde), in the serum and retina, as well as elevated Jagged-1 and reduced DLL-4, Notch-1 and -4 in the retina. All treatments improved retinal outcomes, but nGSH and CoQ10+fish oil co-treatments were most beneficial for improving retinal vascular outcomes, suppressing retinal oxidative stress, reducing retinal Jagged-1, and elevating retinal DLL-4, Notch-1 and Notch-4.

Conclusion(s):

These data show that antioxidants alone and co-administered with lipids are potent modulators of Notch ligands and receptors and may confer beneficial effects in the setting of neonatal IH. Further studies are needed to establish their efficacy for preventing or reducing the severity of retinopathy of prematurity.