美国洛伊医学研究所Marin L. Gantner等研究人员合作发现，丝氨酸和甘氨酸生理学能够可逆地调节视网膜和外周神经功能。该项研究成果于2024年8月26日在线发表在《细胞—代谢》杂志上。

研究人员描述了丝氨酸、甘氨酸和一碳代谢（SGOC）如何在眼睛、肝脏和肾脏中流动，以维持视网膜氨基酸水平和功能。患有黄斑毛细血管扩张症（MacTel）的患者（这是一种与年龄相关的视网膜疾病），其血液中丝氨酸和甘氨酸减少，并携带SGOC代谢酶的有害等位基因，表现出血液中丝氨酸的明显减少。

Phgdh^+/−小鼠模型经历了饮食限制丝氨酸/甘氨酸后视网膜缺陷加速，突显了原本隐性的不全基因型如何影响视网膜健康。研究人员证明，丝氨酸相关的视网膜病和外周神经病是可逆的，因为在小鼠中补充丝氨酸可以恢复这两种病症。这些数据为神经视网膜功能障碍的遗传和代谢驱动因素提供了分子见解，同时突出了改善这一发病机制的治疗机会。

据悉，代谢稳态通过冗余途径维持，以确保在禁食和其他应激条件下的营养供应。这些途径在组织内局部调节，同时通过肝脏、肾脏和循环系统进行全身调节。

附：英文原文

Title: Serine and glycine physiology reversibly modulate retinal and peripheral nerve function

Author: Esther W. Lim, Regis J. Fallon, Caleb Bates, Yoichiro Ideguchi, Takayuki Nagasaki, Michal K. Handzlik, Emeline Joulia, Roberto Bonelli, Courtney R. Green, Brendan R.E. Ansell, Maki Kitano, Ilham Polis, Amanda J. Roberts, Furuya Shigeki, Rando Allikmets, Martina Wallace, Martin Friedlander, Christian M. Metallo, Marin L. Gantner

Issue&Volume: 2024-08-26

Abstract: Metabolic homeostasis is maintained by redundant pathways to ensure adequate nutrient supply during fasting and other stresses. These pathways are regulated locally in tissues and systemically via the liver, kidney, and circulation. Here, we characterize how serine, glycine, and one-carbon (SGOC) metabolism fluxes across the eye, liver, and kidney sustain retinal amino acid levels and function. Individuals with macular telangiectasia (MacTel), an age-related retinal disease with reduced circulating serine and glycine, carrying deleterious alleles in SGOC metabolic enzymes exhibit an exaggerated reduction in circulating serine. A Phgdh+/ mouse model of this haploinsufficiency experiences accelerated retinal defects upon dietary serine/glycine restriction, highlighting how otherwise silent haploinsufficiencies can impact retinal health. We demonstrate that serine-associated retinopathy and peripheral neuropathy are reversible, as both are restored in mice upon serine supplementation. These data provide molecular insights into the genetic and metabolic drivers of neuro-retinal dysfunction while highlighting therapeutic opportunities to ameliorate this pathogenesis.

DOI: 10.1016/j.cmet.2024.07.021

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(24)00323-1