Dipartimento di Farmacia-DIFAR,-Biochemistry Lab., University of Genoa, V.le Benedetto XV 3, 16132 Genova, Italy.
UOC Mutagenesi, IRCCS AOU San Martino - IST (Istituto Nazionale per la Ricerca sul Cancro), Genova, Italy.
Free Radic Biol Med. 2018 Mar;117:110-118. doi: 10.1016/j.freeradbiomed.2018.01.029. Epub 2018 Feb 2.
Oxidative stress is a primary risk factor for both inflammatory and degenerative retinopathies. Our previous data on blue light-irradiated retinas demonstrated an oxidative stress higher in the rod outer segment (OS) than in the inner limb, leading to impairment of the rod OS extra-mitochondrial aerobic metabolism. Here the oxidative metabolism and Reactive Oxygen Intermediates (ROI) production was evaluated in purified bovine rod OS in function of exposure to different illumination conditions. A dose response was observed to varying light intensities and duration in terms of both ROI production and ATP synthesis. Pretreatment with resveratrol, inhibitor of FF-ATP synthase, or metformin, inhibitor of the respiratory complex I, significantly diminished the ROI production. Metformin also diminished the rod OS Complex I activity and reduced the maximal OS response to light in ATP production. Data show for the first time the relationship existing in the rod OS between its -aerobic- metabolism, light absorption, and ROI production. A beneficial effect was exerted by metformin and resveratrol, in modulating the ROI production in the illuminated rod OS, suggestive of their beneficial action also in vivo. Data shed new light on preventative interventions for cone loss secondary to rod damage due to oxidative stress.
氧化应激是炎症性和退行性视网膜病变的主要危险因素。我们之前关于蓝光照射视网膜的研究数据表明，在杆状细胞外节（OS）中的氧化应激比在内部肢中更高，导致杆状细胞 OS 线粒体外需氧代谢受损。在这里，我们评估了在不同光照条件下纯化的牛杆状 OS 中的氧化代谢和活性氧中间体（ROI）的产生。根据 ROI 产生和 ATP 合成的不同，观察到了对不同光强度和持续时间的剂量反应。用白藜芦醇（FF-ATP 合酶抑制剂）或二甲双胍（呼吸复合物 I 抑制剂）预处理，可显著减少 ROI 的产生。二甲双胍还降低了杆状 OS 复合物 I 的活性，并降低了 OS 对光的最大 ATP 产生反应。数据首次显示了杆状 OS 中其 -需氧-代谢、光吸收和 ROI 产生之间的关系。二甲双胍和白藜芦醇发挥了有益的作用，调节了光照下杆状 OS 中的 ROI 产生，提示它们在体内也具有有益的作用。这些数据为由于氧化应激导致的光感受器细胞损失的预防干预措施提供了新的思路。
