Acceleration of age-induced proteolysis in the guinea pig lens nucleus by in vivo exposure to hyperbaric oxygen: A mass spectrometry analysis

• Published in: Experimental eye research 2021-09, Vol.210, p.108697-108697, Article 108697
• Main Authors: Giblin, Frank J., Anderson, David M.G., Han, Jun, Rose, Kristie L., Wang, Zhen, Schey, Kevin L.
• Format: Article
• Language: English
• Subjects: Aging - physiology; Alpha crystallin; alpha-Crystallin A Chain - metabolism; Animals; Aquaporin-0; Aquaporins - metabolism; Cataract - etiology; Cataract - metabolism; Cataract - pathology; Chromatography, Liquid; Crystallins - metabolism; Cytoskeletal Proteins - metabolism; Disease Models, Animal; Eye Proteins - metabolism; Guinea Pigs; Hyperbaric oxygen; Hyperbaric Oxygenation - adverse effects; Lens; Lens Nucleus, Crystalline - metabolism; Lens Nucleus, Crystalline - pathology; Mass spectrometry; Nuclear cataract; Protein truncation; Proteolysis - drug effects; Tandem Mass Spectrometry; αA66-80 peptide
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2021.108697

Hyperbaric oxygen (HBO) treatment of animals or ocular lenses in culture recapitulates many molecular changes observed in human age-related nuclear cataract. The guinea pig HBO model has been one of the best examples of such treatment leading to dose-dependent development of lens nuclear opacities. In this study, complimentary mass spectrometry methods were employed to examine protein truncation after HBO treatment of aged guinea pigs. Quantitative liquid chromatography-mass spectrometry (LC-MS) analysis of the membrane fraction of guinea pig lenses showed statistically significant increases in aquaporin-0 (AQP0) C-terminal truncation, consistent with previous reports of accelerated loss of membrane and cytoskeletal proteins. In addition, imaging mass spectrometry (IMS) analysis spatially mapped the acceleration of age-related αA-crystallin truncation in the lens nucleus. The truncation sites in αA-crystallin closely match those observed in human lenses with age. Taken together, our results suggest that HBO accelerates the normal lens aging process and leads to nuclear cataract. •Guinea pig lens protein truncation is accelerated upon HBO treatment.•Protein truncation was analyzed by LC-MS/MS and imaging mass spectrometry.•Increased truncation of aquaporin-0 occurred in lens nucleus with HBO treatment.•Increased truncation of αA-crystallin localized to lens nucleus upon HBO treatment.