Comparative Effects of Coenzyme Q10 or n-3 Polyunsaturated Fatty Acid Supplementation on Retinal Angiogenesis in a Rat Model of Oxygen-Induced Retinopathy

Abstract

Neonatal intermittent hypoxia (IH) or apnea afflicts 70% to 90% of all preterm infants <28 weeks gestation, and is associated with severe retinopathy of prematurity (ROP). We tested the hypotheses that coenzyme Q10 (CoQ10) or omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplementation during neonatal IH reduces the severity of oxygen-induced retinopathy (OIR). Newborn rats were exposed to two IH paradigms: (1) 50% O2 with brief hypoxia (12% O2); or (2) 21% O2 with brief hypoxia, until postnatal day 14 (P14), during which they received daily oral CoQ10 in olive oil, n-3 PUFAs in fish oil, or olive oil only and compared to room air (RA) treated groups. Pups were examined at P14, or placed in RA until P21. Retinal angiogenesis, histopathology, and morphometry were determined. Both IH paradigms produced severe OIR, but these were worsened with 50/12% O2 IH. CoQ10 and n-3 PUFAs reduced the severity of OIR, as well as ocular growth factors in both IH paradigms, but CoQ10 was more effective in 50/12% O2 IH. Supplementation with either CoQ10 or n-3 PUFAs targeting IH-induced retinal injury is individually effective for ameliorating specific characteristics consistent with ROP. Given the complexity of ROP, further studies are needed to determine whether combined CoQ10 and n-3 PUFAs supplementation would optimize their efficacy and result in a better outcome.

Protective Effects and Molecular Signaling of n-3 Fatty Acids on Oxidative Stress and Inflammation in Retinal Diseases

“…Numerous investigations using the OIR model have shown that n-3 fatty acids administration during the neovascular phase significantly reduces neovascularization without altering vasodilation or normal vessel regeneration [ 109 ]. Their supplementation is a potent modifier of IGF-1 and reduces OIR severity [ 110 ]. n-3 fatty acids suppressed TNF-α expression in the OIR model, decreasing the size of the retinal avascular area [ 74 , 111 ].…”

Bumetanide Suppression of Angiogenesis in a Rat Model of Oxygen-Induced Retinopathy

“…Animals randomized to hyperoxia were exposed to constant 50% O 2 from P0-P14, and animals randomized to IH were exposed to 50% O 2 for 30 min followed by eight IH cycles per day from P0-P14. The IH paradigm was previously described [32][33][34]61] and mimics preterm newborn infants who experience recurrent apnea and desaturations.…”

“…ADPase-stained retinal flatmounts were used to determine the tortuosity index and vessel diameter. For the tortuosity index, a line was traced along the tortuous arteries using the polyline tool compared to a straight line traced from the vessel origin at the optic disk to the branch point using the arbitrary line tool of the CellSens software (Olympus America Inc., Center Valley, PA, USA) as previously described [33,34,60,61]. Vessel diameter at the optic disk was quantified using the arbitrary line tool of the CellSens Dimension software (Olympus America Inc., Center Valley, PA, USA).…”

Current evidence and outcomes for retinopathy of prematurity prevention: insight into novel maternal and placental contributions

“…Furthermore, dietary omega-3 fatty acid supplementation during the proliferative stage of OIR also improved retinal outcome, greatly reducing neovascularization [138]. However, Beharry et al [139], found a higher incidence of peripheral hemorrhaging in omega-3 treated pups, possibly due to the anti-thrombotic effects of PUFAs [140]. ROP outcomes after long-chain polyunsaturated fatty acid supplementation have been tested in preterm infants with largely favorable results.…”