Bashir Sidra, Cai Charles L, Marcelino Matthew, Aranda Jacob V, Beharry Kay D
Department of Pediatrics, Division of Neonatal-Perinatal Medicine, State University of New York Downstate Health Sciences University, Brooklyn, NY 11203, USA.
Medical School, State University of New York Downstate Health Sciences University, Brooklyn, NY 11203, USA.
Pharmaceuticals (Basel). 2024 Mar 17;17(3):381. doi: 10.3390/ph17030381.
Notch ligands and receptors are important for cell specification and angiogenesis, but their role in oxygen-induced retinopathy (OIR) is not well studied. Delta-like ligand (DLL)-4/Notch inhibits angiogenesis, while Jagged-1/Notch promotes angiogenesis. We tested the hypothesis that early supplementation with antioxidants and/or fish oil curtails severe OIR by inducing DLL-4/Notch and reducing Jagged-1/Notch. Newborn rats were exposed to brief intermittent hypoxia (IH) during hyperoxia, during which they received daily oral supplements of (1) fish oil, (2) coenzyme Q10 (CoQ10) in olive oil (OO), (3) glutathione nanoparticles (nGSH), (4) fish oil + CoQ10, or (5) OO (controls) from birth (P0) to P14. At P14, the pups were placed in room air (RA) until P21, with no further treatment. Oxidative stress, apoptosis, ocular histopathology, and Notch signaling were assessed. Neonatal IH resulted in severe retinal damage consistent with retinopathy of prematurity (ROP). Retinal damage was associated with induced oxidative stress and Jagged-1/Notch signaling, as well as reduced DLL-4/Notch signaling. All treatments reversed these outcomes, but nGSH produced the most beneficial outcomes. Severe OIR promoted the induction of Jagged-1/Notch and curtailed DLL-4/Notch, which was an effect that could be reversed with nGSH supplementation. These findings may indicate a potential alternate pathway for ROP treatment and/or prevention.
Notch配体和受体对细胞分化及血管生成很重要，但其在氧诱导性视网膜病变（OIR）中的作用尚未得到充分研究。Delta样配体（DLL）-4/Notch抑制血管生成，而Jagged-1/Notch促进血管生成。我们验证了以下假设：早期补充抗氧化剂和/或鱼油可通过诱导DLL-4/Notch并减少Jagged-1/Notch来减轻严重的OIR。新生大鼠在高氧环境下暴露于短暂间歇性缺氧（IH），在此期间，从出生（P0）到P14，它们每天接受以下口服补充剂：（1）鱼油，（2）橄榄油（OO）中的辅酶Q10（CoQ10），（3）谷胱甘肽纳米颗粒（nGSH），（4）鱼油 + CoQ10，或（5）OO（对照组）。在P14时，将幼崽置于室内空气（RA）中直至P21，不再进行进一步治疗。评估氧化应激、细胞凋亡、眼部组织病理学和Notch信号传导。新生儿IH导致与早产儿视网膜病变（ROP）一致的严重视网膜损伤。视网膜损伤与诱导的氧化应激和Jagged-1/Notch信号传导以及减少的DLL-4/Notch信号传导相关。所有治疗均逆转了这些结果，但nGSH产生了最有益的结果。严重的OIR促进了Jagged-1/Notch的诱导并减少了DLL-4/Notch，而补充nGSH可逆转这种效应。这些发现可能表明ROP治疗和/或预防的潜在替代途径。
