DIPTERIS - University of Genova, Corso Europa 26, 16132 Genova, Italy.
Med Hypotheses. 2012 Apr;78(4):423-7. doi: 10.1016/j.mehy.2011.12.012. Epub 2012 Jan 28.
Vertebrate retinal rods are photoreceptors for dim-light vision. They display extreme sensitivity to light thanks to a specialized subcellular organelle, the rod outer segment. This is filled with a stack of membranous disks, expressing the proteins involved in visual transduction, a very energy demanding process. Our previous proteomic and biochemical studies have shed new light on the chemical energy processes that supply ATP to the outer segment, suggesting the presence of an extra-mitochondrial aerobic metabolism in rod outer segment, devoid of mitochondria, which would account for a quantitatively adequate ATP supply for phototransduction. Here the functional presence of an oxidative phosphorylation in the rod outer limb is examined for its relationship to many physiological and pathological data on the rod outer segment. We hypothesize that the rod outer limb is at risk of oxidative stress, in any case of impairment in the respiratory chain functioning, or of blood supply. In fact, the electron transfer chain is a major source of reactive O(2) species, known to produce severe alteration to the membrane lipids, especially those of the outer segment that are rich in polyunsaturated fatty acids. We propose that the disk membrane may become the target of reactive oxygen species that may be released by the electron transport chain under pathologic conditions. For example, during aging reactive oxygen species production increases, while cellular antioxidant capacity decreases. Also the apoptosis of the rod observed after exposure to bright or continuous illumination can be explained considering that an overfunctioning of phototransduction may damage the disk membrane to a point at which cytochrome c escapes from the intradiskal space, where it is presently supposed to be, activating a putative caspase 9 and the apoptosome. A pathogenic mechanism for many inherited and acquired retinal degenerations, representing a major problem in clinical ophthalmology, is proposed: a number of rod pathologies would be promoted by impairment of energy supply and/or oxidative stress in the rod outer segment. In conclusion we suppose that the damaging role of oxygen, be it hypoxia or hyperoxia invoked in most of the blinding diseases, acquired and even hereditary is to be seeked for inside the photoreceptor outer segment that would conceal a potential for cell death that is still to be recognized.
脊椎动物的视网膜杆状细胞是暗视觉的光感受器。由于一种特殊的亚细胞细胞器，即杆状外节，它们对光具有极高的敏感性。这个细胞器充满了一层膜盘，表达了参与视觉转导的蛋白质，这是一个非常耗能的过程。我们之前的蛋白质组学和生化研究为供应外节的化学能量过程提供了新的认识，表明杆状外节存在一种无线粒体的额外的需氧代谢，它可以为光转导提供足够的 ATP 供应。在这里，我们研究了杆状外肢的氧化磷酸化的功能存在与其对杆状外节的许多生理和病理数据的关系。我们假设，在呼吸链功能障碍或血液供应受损的情况下，杆状外肢容易受到氧化应激的影响。事实上，电子传递链是活性氧（ROS）的主要来源，已知它会严重改变膜脂质，特别是富含多不饱和脂肪酸的外节膜脂质。我们提出，在病理条件下，电子传递链可能会释放活性氧（ROS），这些 ROS 可能会攻击盘膜。例如，随着年龄的增长，活性氧（ROS）的产生增加，而细胞抗氧化能力下降。此外，在暴露于强光或持续光照后观察到的杆状细胞凋亡也可以解释为，过度的光转导可能会损坏盘膜，以至于细胞色素 c 从盘内空间逸出，目前认为细胞色素 c 应该在那里，激活潜在的半胱天冬酶 9 和凋亡体。我们提出了一种针对许多遗传性和获得性视网膜退行性变的致病机制，这是临床眼科的一个主要问题：许多杆状病变是由于杆状外节的能量供应和/或氧化应激受损而促进的。总之，我们假设，在大多数致盲疾病中涉及的缺氧或高氧的氧的破坏作用，无论是获得性的还是遗传性的，都应该在光感受器外节中寻找，外节可能隐藏着尚未被认识到的细胞死亡的潜力。
