Siu Timothy L, Morley John W, Coroneo Minas T
School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
Clin Exp Ophthalmol. 2008 Mar;36(2):176-85. doi: 10.1111/j.1442-9071.2008.01699.x.
The neurosensory retina is a highly specialized sense organ that is subjected to constant exposure of systemic toxins, oxidative stress and focused light rays. Important advances have been made in recent decades in unravelling a myriad of defence mechanisms against such insults and consequently in improving the understanding of the principles underlying various drug- and light-induced disease processes. To defend against circulating toxins, the retina possesses a specialized blood-retinal barrier (BRB) that tightly regulates the transport of substances across the functional boundaries of the retina at the retinal capillaries and the retinal pigmented epithelium. An endogenous cytochrome p450 system is strategically located within the retina to neutralize agents that can diffuse through the BRB. The biooxidation effect of light is prevented by a wide array of unique antioxidant mechanisms in the retina. Nonetheless, pathological processes may evolve when these different lines of defence are overwhelmed by various xenobiotics, environmental agents such as cigarette smoke and excessive light exposure, particularly of short wavelength high frequency blue light and ultraviolet light. Latest research using transgenic models has revealed novel apoptotic pathways implicated in acute phototoxicity, in particular blue light damage, and provides important clues for further understanding the risks of high-frequency light exposure to human retinopathy. This review article summarizes the basic scientific principles of these different defence mechanisms and discuss the implications in pathophysiology and treatment.
神经感觉视网膜是一种高度特化的感觉器官，不断受到全身毒素、氧化应激和聚焦光线的影响。近几十年来，在揭示针对此类损伤的众多防御机制方面取得了重要进展，从而增进了对各种药物和光诱导疾病过程背后原理的理解。为了抵御循环毒素，视网膜拥有一种特殊的血视网膜屏障（BRB），它在视网膜毛细血管和视网膜色素上皮处严格调节物质跨视网膜功能边界的运输。一种内源性细胞色素p450系统战略性地位于视网膜内，以中和可通过BRB扩散的物质。视网膜中一系列独特的抗氧化机制可防止光的生物氧化作用。然而，当这些不同的防御线被各种外源性物质、环境因素（如香烟烟雾）和过度的光线照射（特别是短波长高频蓝光和紫外线）压垮时，病理过程可能会发展。最新的转基因模型研究揭示了与急性光毒性（特别是蓝光损伤）相关的新凋亡途径，并为进一步了解高频光暴露对人类视网膜病变的风险提供了重要线索。这篇综述文章总结了这些不同防御机制的基本科学原理，并讨论了其在病理生理学和治疗方面的意义。
