Regulation of tissue oxygen levels in the mammalian lens
Regulation of tissue oxygen levels in the mammalian lens
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DOI：
10.1113/jphysiol.2004.068619
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发表时间：
2004-09-15
影响因子：
5.5
通讯作者：
Bassnett, S
中科院分区：
文献类型：
--
作者：
McNulty, R;Huan, W;Bassnett, S
晶状体核混浊是导致失明的主要原因，被认为是关键细胞成分氧化的结果。因此，晶状体透明度的长期保持可能有赖于晶状体核内低氧的维持。我们绘制了分离的牛晶状体中溶解氧的分布图，并测量了晶状体或部分晶状体的耗氧率(Q(O2))。为了评价线粒体代谢对晶状体氧收支的影响，我们检测了线粒体抑制剂对晶状体氧平衡的影响。用双光子显微镜观察线粒体在活体晶状体中的分布。我们发现，P-O2在组织内保持着陡峭的梯度，导致核心中的P-O2<；2毫米汞柱。线粒体呼吸约占晶状体耗氧量的90%；然而，P-O2梯度延伸到含线粒体细胞层的边界之外，表明存在非线粒体耗氧者。根据扩散-消耗模型计算了晶状体不同区域的氧消耗时间常数和有效氧扩散系数。典型的扩散系数为3×10~(-5)cm~(-2)，有效扩散系数为S~(-1)，耗氧量为5min。令人惊讶的是，计算出的时间常数在含有线粒体的分化纤维(DF)和不含线粒体的成熟纤维(MF)之间没有区别。根据这些参数，DF细胞约占晶状体耗氧量的88%。组织温度的适度降低导致Q(O2)显著降低，随后晶状体核心充氧。这一现象可能与临床相关，因为在眼内手术中，冷的富氧溶液经常被注入眼睛。这样的手术与术后核性白内障的发病率高得惊人。
Opacification of the lens nucleus is a major cause of blindness and is thought to result from oxidation of key cellular components. Thus, long-term preservation of lens clarity may depend on the maintenance of hypoxia in the lens nucleus. We mapped the distribution of dissolved oxygen within isolated bovine lenses and also measured the rate of oxygen consumption (Q(O2)) by lenses, or parts thereof. To assess the contribution of mitochondrial metabolism to the lens oxygen budget, we tested the effect of mitochondrial inhibitors on 00, and partial pressure of oxygen (P-O2). The distribution of mitochondria was mapped in living lenses by 2-photon microscopy. We found that a steep gradient of P-O2 was maintained within the tissue, leading to P-O2 < 2 mmHg in the core. Mitochondrial respiration accounted for approximately 90% of the oxygen consumed by the lens; however, P-O2 gradients extended beyond the boundaries of the mitochondria-containing cell layer, indicating the presence of non-mitochondrial oxygen consumers. Time constants for oxygen consumption in various regions of the lens and an effective oxygen diffusion coefficient were calculated from a diffusion-consumption model. Typical values were 3 x 10(-5) cm(2) s(-1) for the effective diffusion coefficient and a 5 min time constant for oxygen consumption. Surprisingly, the calculated time constants did not differ between differentiating fibres (DF) that contained mitochondria and mature fibres (MF) that did not. Based on these parameters, DF cells were responsible for approximately 88% of lens oxygen consumption. A modest reduction in tissue temperature resulted in a marked decrease in Q(O2) and the subsequent flooding of the lens core with oxygen. This phenomenon may be of clinical relevance because cold, oxygen-rich solutions are often infused into the eye during intraocular surgery. Such procedures are associated with a strikingly high incidence of postsurgical nuclear cataract.