Oxygen Distribution in the Rabbit Eye and Oxygen Consumption by the Lens

Shui, Ying-Bo; Fu, Jia-Jan; Garcia, Claudia M.; Dattilo, Lisa K.; Rajagopal, Ramya; McMillan, Sam; Mak, Garbo; Holekamp, Nancy M.; Lewis, Angie; Beebe, David C.

doi:10.1167/iovs.05-1475

Cited by 126 publications

(125 citation statements)

References 33 publications

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“…Microelectrode studies demonstrated that much of this oxygen was consumed by the nearby retina, thereby creating an oxygen gradient in the vitreous near the surface of the retina (figure 2a) [19]. Measurements in human and rabbit eyes showed that oxygen was low in the central vitreous and near the lens [21,27,37].…”

Section: The Mechanisms That Maintain the Low-oxygen Environment Aroumentioning

confidence: 99%

Vitreoretinal influences on lens function and cataract

Beebe

Holekamp

Siegfried

et al. 2011

Phil. Trans. R. Soc. B

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The lens is composed of a thin metabolically active outer layer, consisting of epithelial and superficial fibre cells. Lying within this outer shell are terminally differentiated, metabolically inactive fibre cells, which are divided into an outer cortex and central nucleus. Mature fibre cells contain a very high protein concentration, which is important for the transparency and refractive power of the lens. These proteins are protected from oxidation by reducing substances, like glutathione, and by the low-oxygen environment around the lens. Glutathione reaches the mature fibre cells by diffusing from the metabolically active cells at the lens surface. With age, the cytoplasm of the nucleus becomes stiffer, reducing the rate of diffusion and making nuclear proteins more susceptible to oxidation. Low pO 2 is maintained at the posterior surface of the lens by the physical and physiological properties of the vitreous body, the gel filling the space between the lens and the retina. Destruction or degeneration of the vitreous body increases exposure of the lens to oxygen from the retina. Oxygen reaches the lens nucleus, increasing protein oxidation and aggregation and leading to nuclear cataract. We suggest that maintaining low pO 2 around the lens should prevent the formation of nuclear cataracts.

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Section: The Mechanisms That Maintain the Low-oxygen Environment Aroumentioning

confidence: 99%

Vitreoretinal influences on lens function and cataract

Beebe

Holekamp

Siegfried

et al. 2011

Phil. Trans. R. Soc. B

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“…Genetic and environmental stresses combined with age are considered as leading contributors to aggregation, crystalline modification and pathogenesis in lens oxidation. The ciliary body and blood vessels of the iris supply glucose and oxygen (O 2 ) to the lens, where it is present in a hypoxic environment containing 0.5-2.3% O 2 (2)(3)(4). The level of O 2 is a very important factor in cataract, and various cataractogenic stressors such as hypoxia, hypoxic conditions along with a low glucose level (5) or high glucose level (6), homocysteine (7), and galactose (6) are found to induce stress in the endoplasmic reticulum (ER), thereby mediating the activation of the unfolded protein response (UPR) along with the production of reactive oxygen species (ROS), which is usually abnormally increased, and lens epithelial cell (LEC) death (3,8,9).…”

Section: Introductionmentioning

confidence: 99%

Attenuation of oxygen fluctuation-induced endoplasmic reticulum stress in human lens epithelial cells

Zheng

Chen

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Cataractogenic stresses are associated with the induction of endoplasmic reticulum (ER) stress. However, little is known about oxygen (O 2 )-induced ER stress in the lens. Cataract research has focused on elevated levels of O 2 in lens epithelial cells (LECs). Excessive levels or a lack of O 2 are known to induce ER stress whereas chronic ER stress activates the unfolded protein response (UPR). The present study investigated the hypothesis that the fluctuation of O 2 levels induces a UPR, and may be controlled by maintaining human LECs (hLECs) in a specific concentration of O 2 . Human LECs were cultured in different atmospheric levels of O 2 . Hypoxic conditions were determined by the level of hypoxia-inducible factor (HIF)-1α. 2',7'-Dichlorodihydrofluorescein diacetate and ethidium homodimer-1 staining were conducted to detect reactive oxygen species (ROS) and cell death, respectively. Protein blot analyses were performed with antibodies specific to antioxidant and UPR-specific proteins. Reverse transcription-quantitatative polymerase chain reaction assays were performed to quantify the mRNA levels of activated NF-E2-related factor 2 (Nrf2) and kelch-like ECH-associated protein 1 (Keap1). The treatment of human LECs with 0 and 20% atmospheric O 2 activated Nrf2/Keap1. The LECs shifted to 1% atmospheric O 2 from 0, 4 or 20% for 24 h showed decreased levels of Keap1. By contrast, hLECs cultured in 1% atmospheric O 2 for 24 h and then shifted to 0, 4 or 20% O 2 exhibited a significant upregulation of Nrf2. These results suggest that oxidative stress proteins were not expressed in a 1% O 2 environment. The O 2 levels in the culture medium were equilibrated within 2 h in the cell culture plates. These results showed that an appropriate oxygen environment for the culture of LECs is ~1 % atmospheric O 2 . Either 0 or 20% of atmospheric O 2 activated the UPR and the Nrf2/Keap1-mediated antioxidant system in LECs and chronic exposure to O 2 fluctuation led to ROS production and cell death. This study revealed that O 2 fluctuation-induced UPR/ER stress could be prevented by maintaining the cells in a 1% O 2 environment.

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“…Most data regarding oxygen kinetics in the anterior chamber of the eye originate from indirect fluid measurements, including the application of polarographic electrode analysis inside the eye (2,4,5,12,13) or on the corneal surface (14) , ocular scanning fluorometry (15) , or optical oxygen sensors (16) and from direct measurements of the AH, using a blood-gas analyzer, obtained via anterior chamber paracentesis (6,17) . To the best of our knowledge, no data of simultaneous evaluations of the PO 2 , PCO 2 , and pH of AH and arterial blood samples exist.…”

Section: Introductionmentioning

confidence: 99%

Blood gas analyzer utility in evaluating oxygen kinetics of the aqueous humor

Erşan

Arıkan

Toman

et al. 2015

Arquivos Brasileiros De Oftalmologia

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Purpose: To measure the partial pressure of oxygen (PO 2 ) and carbon dioxide (PCO 2 ) and the pH of aqueous humor (AH) and arterial blood samples from rabbits using a blood gas analyzer. Methods: Twenty New Zealand rabbits were anesthetized intramuscularly with ketamine and xylazine and were then allowed to breathe room air. Using a gas blood analyzer, arterial blood and AH samples were analyzed for PO 2 , PCO 2 , and pH. Results: The mean arterial blood pressure was 87.14 ± 15.0 mmHg. The mean blood and AH PO 2 were 95.18 ± 11.76 mmHg and 88.83 ± 9.92 mmHg, the mean blood and AH PCO 2 were 25.86 ± 5.46 mmHg and 29.50 ± 5.36 mmHg, and the mean blood and AH pH were 7.38 ± 0.06 and 7.33 ± 0.09, respectively. Conclusions: The blood gas analyzer was easily employed to evaluate the aqueous humor in rabbits. When comparing the results of studies evaluating aqueous PO 2 , care should be taken to determine the methods used in these studies.

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Oxygen Distribution in the Rabbit Eye and Oxygen Consumption by the Lens

Cited by 126 publications

References 33 publications

Vitreoretinal influences on lens function and cataract

Vitreoretinal influences on lens function and cataract

Attenuation of oxygen fluctuation-induced endoplasmic reticulum stress in human lens epithelial cells

Blood gas analyzer utility in evaluating oxygen kinetics of the aqueous humor

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