Regulation of tissue oxygen levels in the mammalian lens
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 ofâ lens clarity may depend on the maintenance of hypoxia in the lens nucleus. We mapped the distribution of dissolved oxygen within isol...
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Published in | The Journal of physiology Vol. 559; no. 3; pp. 883 - 898 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
9600 Garsington Road , Oxford , OX4 2DQ , UK
The Physiological Society
15.09.2004
Blackwell Science Ltd Blackwell Science Inc |
Subjects | |
Online Access | Get full text |
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Summary: | 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 ofâ 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 ( [Qdot] O 2 ) 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 [Qdot] O 2 and partial pressure of oxygen ( P O 2 ). The distribution of mitochondria was mapped in living lenses by 2-photon microscopy. We found that a steep gradient of
P O 2 was maintained within the tissue, leading to P O 2 < 2 mmHg in the core. Mitochondrial respiration accounted for approximately 90% of the oxygen consumed by the lens; however,
P O 2 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 diffusionâconsumption model. Typical values were 3 Ã 10 â5 cm 2 s â1 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 [Qdot] O 2 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-3751 1469-7793 |
DOI: | 10.1113/jphysiol.2004.068619 |