Now this is some futuristic medicine, I have to say (commentary here at Cell). The authors are looking at “dry eye disease” (keratoconjunctivitis sicca), which can have a rather complex biological background. There are quite a few contributing causes (contact lens use, aging, clogged oil glands, decreased tear production overall, and more). But a common feature that most of these lead to is a chronic inflammation/oxidative stress condition in the eye tissue, and like most of these situations, it can be a self-worsening condition over time as damage leads to more damage.不得不说，这确实是某种充满未来感的医学（此处为《细胞》杂志的评论）。作者们研究的是“干眼症”（角结膜干燥症），其生物学背景相当复杂。导致该病的诱因有很多（如佩戴隐形眼镜、衰老、睑板腺堵塞、泪液分泌减少等）。但这些诱因大多会导致一个共同特征，即眼部组织的慢性炎症和氧化应激；正如大多数此类情况一样，随着损伤不断加剧，病情可能会随时间推移而恶化。
The authors are hoping that extra NADPH would help to interrupt this cycle. That’s a universal reducing agent in a whole range of cellular processes, and the authors suggest that its supplementation in eye tissue and the resutling antioxidant effect could restore redox balance and reduce the presence of reactive oxygen species in the inflamed tissues. That’s a reasonable idea, but how do you get this on site where it’s needed? Here’s their answer, which I’m pretty sure will not have occurred to anyone in the audience: engineer a thylakoid-like system (based on what plants use as their organ of photosynthesis) and allow photosynthetic production of extra NADPH and ATP in the eye tissue (which is being bathed in light anyway, right?)作者们希望额外的 NADPH 有助于打破这一循环。NADPH 是一系列细胞过程中通用的还原剂，作者认为，在眼部组织中补充 NADPH 并由此产生的抗氧化效应，可以恢复氧化还原平衡，并减少炎症组织中活性氧的含量。这是一个合理的想法，但如何将其送达所需的部位呢？以下是他们的方案，我敢肯定在座的各位绝对没想过：构建一种类似类囊体的系统（基于植物光合作用的器官），让眼部组织（反正也沐浴在光线下，对吧？）通过光合作用产生额外的 NADPH 和 ATP。
A bold strategy! The closest thing in the animal kingdom is probably a group of sea slugs that latch onto the chloroplasts found in the algae that they eat and sequester them in their own intestinal cells, where they are used as backup ATP food producers when normal prey are running low. That’s rather distant from the human eyeball, but at the same time it does make one think that running some sort of cross-kingdom collaboration between animals and plants is not prima facie crazy, either. In fact, it’s been tried a few times for inflammatory conditions like arthritis, but those attempts have been understandably hampered by the need to get around the fact that there’s not much light inside (say) the knee joint. The eye seems to be a bit more straightforward shot on goal.这是一个大胆的策略！在动物界，最接近的例子可能是一群海蛞蝓，它们会摄取所食藻类中的叶绿体，并将其储存在自己的肠道细胞中，在缺乏常规食物时作为 ATP 的备用能量来源。这与人类眼球相去甚远，但同时也让人觉得，进行某种跨界（动物与植物之间）的合作并非异想天开。事实上，针对关节炎等炎症，人们曾尝试过几次，但这些尝试不可避免地受到了限制，因为（比如）膝关节内部缺乏光照。而眼睛似乎是一个更直接的目标。
The paper describes isolation of a stripped-down thylakoid-like unit from spinach leaves, which nanostructures have lost most of their light-independent (and NADPH-consuming) co-enzymes such as the famous RuBisCO. They name this LEAF (light-reaction enriched thylakoid NADPH-foundry). In experiments with macrophage surrogate cells, which took these LEAFs up by endocytosis, these seem to be able to provide sufficient NADPH (by conversion from NADP+) to mammalian cells when their own NADPH-generating systems are deliberately blocked. These effects were also seen in immortalized human corneal epithelium cells, which also internalized the LEAF structures. When this was done on deliberately stressed cells, NADPH increased and reactive oxygen species went down along with other markers of inflammation. The LEAFs persisted intracellularly for unexpected long periods, and are apparently not just automatically routed to lysosomal compartments for destruction.该论文描述了从菠菜叶中分离出一种精简的类囊体单元，这些纳米结构已经失去了大部分光独立（且消耗 NADPH）的辅酶，例如著名的 RuBisCO。他们将其命名为 LEAF（光反应富集类囊体 NADPH 工厂）。在以巨噬细胞替代细胞进行的实验中，这些细胞通过内吞作用摄取了 LEAF，当哺乳动物细胞自身的 NADPH 生成系统被刻意阻断时，LEAF 似乎能够为其提供充足的 NADPH（通过 NADP+ 转化而来）。在同样摄取了 LEAF 结构的人类永生化角膜上皮细胞中也观察到了这些效果。当对处于压力状态的细胞进行处理时，NADPH 水平升高，活性氧以及其他炎症标志物水平下降。LEAF 在细胞内停留的时间出奇地长，而且显然不会被自动送往溶酶体进行降解。
When these two types of cells were grown in a “transwell” setup (physically separated by a porous membrane but in the same culture fluid), it appeared that introducing LEAFs into the macrophage-cell side showed normalizing effects on the corneal epithelium side as well, which is encouraging. It appears that the LEAF structures have useful effects both inside and outside the cells, and that releasing more NADPH in general into either environment is beneficial. And these effects translated all the way to topical administration in the eyes of rats (and the benefits were light-dependent, as you would figure).当这两种细胞在“小室”（transwell）装置中培养时（通过多孔膜物理隔离，但在同一培养液中），引入 LEAF 到巨噬细胞侧似乎对角膜上皮细胞侧也产生了调节作用，这令人鼓舞。看来 LEAF 结构在细胞内外都能发挥有益作用，而在任何环境中释放更多的 NADPH 都是有益的。这些效果甚至转化为了大鼠眼部的局部给药（正如你所料，这些益处具有光依赖性）。
So all this makes you wonder if some sort of “LEAF eyedrop) could alleviate dry eye to an extent that other therapies can’t realize. As it stands, it looks like things start dropping off on a time scale of hours, which is inconvenient but not a show-stopper. But this are early results: can such structures be made to persist longer, even within cells? If they do, where will they go during mitosis? Are there ways to make them associate with particular organelles like the mitochondria or the ER? These are rather odd things to be thinking about, but I’m glad that someone is.这一切不禁让人联想，某种“LEAF 眼药水”是否能缓解其他疗法无法解决的干眼症。目前看来，其效果在几小时的时间尺度内会逐渐减弱，这虽然不方便，但并非不可克服。但这只是早期结果：能否让这些结构在细胞内存在更长时间？如果可以，它们在有丝分裂期间会去向何处？有没有办法让它们与线粒体或内质网等特定细胞器结合？这些想法虽然有些离奇，但我很高兴有人在研究它们。
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