Department of Ophthalmology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Center for Brain Science, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Nutrients. 2022 Mar 23;14(7):1333. doi: 10.3390/nu14071333.
There is a gap in understanding the effect of the essential ω-3 and ω-6 long-chain polyunsaturated fatty acids (LCPUFA) on Phase I retinopathy of prematurity (ROP), which precipitates proliferative ROP. Postnatal hyperglycemia contributes to Phase I ROP by delaying retinal vascularization. In mouse neonates with hyperglycemia-associated Phase I retinopathy, dietary ω-3 (vs. ω-6 LCPUFA) supplementation promoted retinal vessel development. However, ω-6 (vs. ω-3 LCPUFA) was also developmentally essential, promoting neuronal growth and metabolism as suggested by a strong metabolic shift in almost all types of retinal neuronal and glial cells identified with single-cell transcriptomics. Loss of adiponectin (APN) in mice (mimicking the low APN levels in Phase I ROP) decreased LCPUFA levels (including ω-3 and ω-6) in retinas under normoglycemic and hyperglycemic conditions. ω-3 (vs. ω-6) LCPUFA activated the APN pathway by increasing the circulating APN levels and inducing expression of the retinal APN receptor. Our findings suggested that both ω-3 and ω-6 LCPUFA are crucial in protecting against retinal neurovascular dysfunction in a Phase I ROP model; adequate ω-6 LCPUFA levels must be maintained in addition to ω-3 supplementation to prevent retinopathy. Activation of the APN pathway may further enhance the ω-3 and ω-6 LCPUFA's protection against ROP.
人们对于必需的 ω-3 和 ω-6 长链多不饱和脂肪酸（LCPUFA）对早产儿视网膜病变（ROP）Ⅰ期的影响存在认识上的差距，这种病变会引发增殖性 ROP。出生后高血糖通过延迟视网膜血管化而导致 ROPⅠ期。在伴有高血糖的 ROPⅠ期的新生小鼠中，饮食中补充 ω-3（与 ω-6 LCPUFA 相比）可促进视网膜血管发育。然而，ω-6（与 ω-3 LCPUFA 相比）也是发育所必需的，这一点可从单细胞转录组学鉴定的几乎所有类型的视网膜神经元和神经胶质细胞的强烈代谢转变中得到提示，其促进了神经元的生长和代谢。在小鼠中缺失脂联素（APN）（模拟 ROPⅠ期的低 APN 水平）会降低视网膜中的 LCPUFA 水平（包括 ω-3 和 ω-6），无论在正常血糖和高血糖条件下均如此。ω-3（与 ω-6 相比）LCPUFA 通过增加循环 APN 水平并诱导视网膜 APN 受体的表达来激活 APN 途径。我们的研究结果表明，在 ROPⅠ期模型中，ω-3 和 ω-6 LCPUFA 对于保护视网膜神经血管功能均至关重要；除了补充 ω-3 之外，还必须维持足够的 ω-6 LCPUFA 水平，以防止发生视网膜病变。激活 APN 途径可能会进一步增强 ω-3 和 ω-6 LCPUFA 对 ROP 的保护作用。
