Lim Julie C, Umapathy Ankita, Grey Angus C, Vaghefi Ehsan, Donaldson Paul J
Department of Physiology, University of Auckland, Auckland, New Zealand; School of Medical Sciences, University of Auckland, New Zealand; New Zealand National Eye Centre, University of Auckland, New Zealand.
Department of Physiology, University of Auckland, Auckland, New Zealand; School of Medical Sciences, University of Auckland, New Zealand; New Zealand National Eye Centre, University of Auckland, New Zealand.
Exp Eye Res. 2017 Mar;156:117-123. doi: 10.1016/j.exer.2016.05.027. Epub 2016 Jun 6.
Outside the traditional roles of the lens as an important refractive element and a UV filter, it was David Beebe's group that first demonstrated that the lens acts an oxygen sink that protects the tissues of the anterior segment of the eye from oxygen or oxygen metabolites. In this review, we follow on from this work, and present new evidence from our laboratory to demonstrate that the lens serves as a reservoir for the release of the antioxidant glutathione (GSH) into the aqueous humor to provide a source of GSH and/or its precursor amino acids to nearby tissues that interface with the aqueous humor, or to remove toxic metabolites from the eye via the aqueous outflow pathway. In addition to GSH release, our laboratory and others have shown that ATP is released from the lens under hyposmotic conditions to activate purinergic signalling pathways in an autocrine manner to alter lens function. In this review, we raise the idea that ATP and/or its subsequent degradation product adenosine may exert a paracrine function and influence purinergic signalling systems in other tissues to alter aqueous humor outflow. These new secondary roles indicate that the lens is not just a passive optical element, but a highly dynamic and active tissue that interacts with its neighbouring tissues, through modifying the environments in which these tissues function. We believe that the lens actively contributes to the ocular environment and as a consequence, removal of the lens would alter the functionality of neighbouring tissues. We speculate that a long term effect of lens removal may be to inadvertently increase the exposure of anterior tissues of the eye to oxidative stress due to elevated oxygen levels and a reduction in the availability of GSH and purinergic signalling molecules in the aqueous humor. Since cataract surgery is now being performed on younger patients due to our increasing diabetic population, over time, we predict these changes may increase the susceptibility of these tissues to oxidative stress and the incidence of subsequent ocular pathologies. If our view of the lens is correct, the actual loss of the biological lens may have longer term consequences for overall ocular health than currently appreciated.
除了晶状体作为重要屈光元件和紫外线滤光器的传统作用外,大卫·比贝的研究小组首次证明,晶状体充当氧气吸收器,保护眼前节组织免受氧气或氧代谢产物的影响。在本综述中,我们延续这项工作,并展示我们实验室的新证据,以证明晶状体作为一个储存库,可将抗氧化剂谷胱甘肽(GSH)释放到房水中,为与房水接触的附近组织提供GSH和/或其前体氨基酸来源,或通过房水流出途径从眼中清除有毒代谢产物。除了GSH释放外,我们实验室和其他研究表明,在低渗条件下,ATP从晶状体释放,以自分泌方式激活嘌呤能信号通路,从而改变晶状体功能。在本综述中,我们提出ATP和/或其后续降解产物腺苷可能发挥旁分泌功能,并影响其他组织中的嘌呤能信号系统,以改变房水流出。这些新的次要作用表明,晶状体不仅是一个被动的光学元件,而且是一个高度动态和活跃的组织,通过改变这些组织发挥功能的环境与其相邻组织相互作用。我们认为,晶状体积极地对眼内环境做出贡献,因此,摘除晶状体将改变相邻组织的功能。我们推测,晶状体摘除的长期影响可能是由于氧气水平升高以及房水中GSH和嘌呤能信号分子可用性降低,无意中增加了眼前部组织对氧化应激的暴露。由于糖尿病患者数量不断增加,现在年轻患者也在接受白内障手术,随着时间的推移,我们预测这些变化可能会增加这些组织对氧化应激的易感性以及随后眼部疾病的发生率。如果我们对晶状体的看法正确,那么生物晶状体的实际丧失对整体眼部健康的长期影响可能比目前所认识到的更大。