Characterization of the Effects of Hyperbaric Oxygen on the Biochemical and Optical Properties of the Bovine Lens

Lim, Julie C.; Vaghefi, Ehsan; Li, Bo; Nye-Wood, Mitchell G.; Donaldson, Paul J.

doi:10.1167/iovs.16-19142

Cited by 18 publications

(15 citation statements)

References 32 publications

(59 reference statements)

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“…Nevertheless, we observed a reduction in the spatial distribution and signal level of GSH, and an increase in the signal level of GSSG in the lens cortex following HBO treatment that is consistent with results using alternative techniques from similar experimental procedures (Giblin et al, 1988). Together these results indicate that HBO treatment of bovine lenses, an experimental approach that has been validated biochemically and optically as a model for lens aging (Lim et al, 2016), elicits metabolic changes detectable by MALDI mass spectrometry that are associated with aging and ARN cataract formation.…”

Section: Discussionmentioning

confidence: 69%

“…1970), we did not detect free L-cysteine since the collected mass range did not include the predicted m/z of L-cysteine. Since previous analyses have shown protein-thiol mixed disulfide formation is increased following HBO treatment (Giblin et al, 1995; Lim et al, 2016), it is likely that the dramatic decrease in CySSG signal in the HBO lens inner cortex is contributing to their formation. Further investigation of the distribution of free L-cysteine in HBO-treated lenses to investigate these hypotheses is ongoing.…”

Section: Discussionmentioning

confidence: 97%

“…1) (Lou, 2003; Lou et al, 1990; Lou et al, 1986; Truscott, 2005). In the bovine lens GSH concentration reaches ~8µmol/g in the outer cortex, and ~1 µmol/g in the nucleus (Lim et al, 2016). The high concentration in the outer cortex is maintained via a combination of GSH uptake, de novo synthesis from its precursor amino acids (cysteine, glutamate and glycine) and GSH regeneration from glutathione disulfide (GSSG), the oxidised form of GSH, via NADPH-based reduction.…”

Section: Introductionmentioning

confidence: 99%

“…Biochemical assays have revealed a decreased GSH:GSSG ratio and elevated levels of oxidative stress markers and lens protein glutathionylation (Cappiello et al, 1995; Lim et al, 2016). Fifteen-hour exposure to HBO induces changes to lens refractive index and optical power, while five-hour exposure is sufficient to induce changes to GSH and GSSG concentrations (Lim et al, 2016). Quantitative data therefore exist, however spatial information remains limited to comparing nuclear and cortical homogenates.…”

Section: Introductionmentioning

confidence: 99%

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Spatial distributions of glutathione and its endogenous conjugates in normal bovine lens and a model of lens aging

Nye-Wood

Spraggins

Caprioli

et al. 2017

Experimental Eye Research

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Glutathione (GSH) is the archetypal antioxidant, and plays a central role in the protection of the ocular lens from cataract formation. High levels of GSH are maintained in the transparent lens, but with advancing age, GSH levels fall in the lens nucleus relative to outer cortical cells, thereby exposing the nucleus of the lens to the damaging effects of oxygen radicals, which ultimately leads to age-related nuclear (ARN) cataract. Under normal conditions, GSH also forms endogenous conjugates to detoxify the lens of reactive cellular metabolites and to maintain cell homeostasis. Due to the intrinsic gradient of lens fibre cell age, the lens contains distinct regions with different metabolic requirements for GSH. To investigate the impact of fibre cell and lens aging on the varied roles that GSH plays in the lens, we have utilised high mass resolution MALDI mass spectrometry profiling and imaging analysis of lens tissue sections. High Dynamic Range (HDR)-MALDI FTICR mass spectrometry was used as an initial screening method to detect regional differences in lens metabolites from normal bovine lenses and in those subjected to hyperbaric oxygen as a model of lens aging. Subsequent MALDI imaging analysis was used to spatially map GSH and its endogenous conjugates throughout all lenses. Accurate mass measurement by MALDI FTICR analysis and LC-MS/MS mass spectrometry of lens region homogenates were subsequently used to identify endogenous GSH conjugates. While the distribution and relative abundance of GSH-related metabolic intermediates involved in detoxification pathways remained relatively unchanged upon HBO treatment, those involved in its antioxidant function were altered under conditions of oxidative stress. For example, reduced glutathione levels were decreased in the lens cortex while oxidised glutathione levels were elevated in the lens outer cortex upon HBO treatment. Interestingly, cysteineglutathione disulfide, was detected in the inner cortex of the normal lens, but was greatly decreased in the HBO-treated lenses. These results contribute to our understanding of the multiple roles that GSH plays in maintenance of lens transparency and in the age-related metabolic changes that lead to lens cataract formation.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Spatial distributions of glutathione and its endogenous conjugates in normal bovine lens and a model of lens aging

Nye-Wood

Spraggins

Caprioli

et al. 2017

Experimental Eye Research

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“…However, in principle, the three-dimensional lamellar structure of the lens could be included in more physically realistic models which, if they also incorporated the internal refractive index gradient of the lens, would be suitable for optical modeling. Promisingly, optical models are now being combined with data on lens physiological properties, to predict visual outcomes of metabolic perturbations (Donaldson et al, 2017; Lim et al, 2016). Thus, converging mathematical and physical models offer the exciting prospect of achieving one of the holy grails of lens research, forging a meaningful connection between the biology of living lens cells and the quality of the final image on the retina.…”

Section: Summary and Future Directionsmentioning

confidence: 99%

The lens growth process

Bassnett

Šikić

2017

Progress in Retinal and Eye Research

102

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The factors that regulate the size of organs to ensure that they fit within an organism are not well understood. A simple organ, the ocular lens serves as a useful model with which to tackle this problem. In many systems, considerable variance in the organ growth process is tolerable. This is almost certainly not the case in the lens, which in addition to fitting comfortably within the eyeball, must also be of the correct size and shape to focus light sharply onto the retina. Furthermore, the lens does not perform its optical function in isolation. Its growth, which continues throughout life, must therefore be coordinated with that of other tissues in the optical train. Here, we review the lens growth process in detail, from pioneering clinical investigations in the late nineteenth century to insights gleaned more recently in the course of cell and molecular studies. During embryonic development, the lens forms from an invagination of surface ectoderm. Consequently, the progenitor cell population is located at the surface and differentiated cells are confined to the interior. The interactions that regulate cell fate thus occur within the obligate ellipsoidal geometry of the lens. In this context, mathematical models are particularly appropriate tools with which to examine the growth process. In addition to identifying key growth determinants, such models constitute a framework for integrating cell biological and optical data, helping clarify the relationship between gene expression in the lens and image quality at the retinal plane.

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Aging of the eye: Lessons from cataracts and age-related macular degeneration

Cvekl,

Vijg

2024

Ageing Research Reviews

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Characterization of the Effects of Hyperbaric Oxygen on the Biochemical and Optical Properties of the Bovine Lens

Abstract: This system may serve as a model to study changes that occur with advanced aging rather than nuclear cataract formation per se.

Cited by 18 publications

References 32 publications

Spatial distributions of glutathione and its endogenous conjugates in normal bovine lens and a model of lens aging

Spatial distributions of glutathione and its endogenous conjugates in normal bovine lens and a model of lens aging

The lens growth process

Aging of the eye: Lessons from cataracts and age-related macular degeneration

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