Fluorescence Studies of Lens Epithelial Cells and Their Constituents

Atherton, Stephen J.; Lambert, C.; Schultz, Joanne; Williams, Natalie; Zigman, Seymour

doi:10.1111/j.1751-1097.1999.tb08289.x

Cited by 24 publications

(18 citation statements)

References 15 publications

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“…The cellular concentration of NADPH is in the μM range, but has been found to be higher in ocular tissues, probably because of the presence of abundant NADPH-dependent “enzyme-crystallins” in the cornea and lens. 82 NADPH functions as an antioxidant in the cornea via multiple mechanisms: 1) It is a coenzyme of GR in the GPX/GR system for the regeneration of GSH from GSSG 83 ; 2) It may act as a direct antioxidant by reducing glutathiyl, tyrosyl, and peroxynitrite radicals generated during oxidative stress 84 ; 3) It is a UVR filter 85 ; 4) It may protect other antioxidant enzymes from ROS-induced inactivation 86 ; and, 5) It maintains a reducing potential for pyridine nucleotide-dependent redox-active enzymes, such as isocitrate dehydrogenase, malic dehydrogenase and 6-phosphate dehydrogenase, which are involved in protecting eye tissues. 87 …”

Section: Antioxidants In the Corneamentioning

confidence: 99%

Antioxidant Defenses in the ocular surface

2009

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The human eye is subjected constantly to oxidative stress due to daily exposure to sunlight, high metabolic activities, and oxygen tension. Reactive oxygen species generated from environmental insults and pathological conditions render the human eye particularly vulnerable to oxidative damage. The ocular surface composed of the tear film, the cornea, and the aqueous humor forms the first physical and biochemical barrier of the eye and plays a pivotal role in combating free radicals. These ocular compartments are enriched in certain antioxidants in the form of metabolic enzymes or small molecules. Such an antioxidant defense system in the ocular surface is essential for the maintenance of redox homeostasis in the eye and protection against oxidative damage. Herein, we review the properties and functions of key constituent antioxidants of the ocular surface.

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Section: Antioxidants In the Corneamentioning

confidence: 99%

Antioxidant Defenses in the ocular surface

2009

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“…Recent studies in our laboratory with Aldh3a1 null mice clearly demonstrate that the lack of ALDH3A1 expression in the cornea results in opacification of the lens [7]. Furthermore, the UV absorbing capacity of ALDH3A1 may be intensified when bound to NAD(P)H [8], which also displays strong absorption in the near UV range. It is therefore reasonable to speculate that ALDH3A1 largely contributes to the UV-absorption properties of the cornea.…”

Section: Introductionmentioning

confidence: 97%

Structural and Functional Modifications of Corneal Crystallin ALDH3A1 by UVB Light

et al. 2010

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As one of the most abundantly expressed proteins in the mammalian corneal epithelium, aldehyde dehydrogenase 3A1 (ALDH3A1) plays critical and multifaceted roles in protecting the cornea from oxidative stress. Recent studies have demonstrated that one protective mechanism of ALDH3A1 is the direct absorption of UV-energy, which reduces damage to other corneal proteins such as glucose-6-phosphate dehydrogenase through a competition mechanism. UV-exposure, however, leads to the inactivation of ALDH3A1 in such cases. In the current study, we demonstrate that UV-light caused soluble, non-native aggregation of ALDH3A1 due to both covalent and non-covalent interactions, and that the formation of the aggregates was responsible for the loss of ALDH3A1 enzymatic activity. Spectroscopic studies revealed that as a result of aggregation, the secondary and tertiary structure of ALDH3A1 were perturbed. LysC peptide mapping using MALDI-TOF mass spectrometry shows that UV-induced damage to ALDH3A1 also includes chemical modifications to Trp, Met, and Cys residues. Surprisingly, the conserved active site Cys of ALDH3A1 does not appear to be affected by UV-exposure; this residue remained intact after exposure to UV-light that rendered the enzyme completely inactive. Collectively, our data suggest that the UV-induced inactivation of ALDH3A1 is a result of non-native aggregation and associated structural changes rather than specific damage to the active site Cys.

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“…NADPH may also function as a direct antioxidant by reducing glutathiyl and tyrosyl radicals generated during oxidative stress (12). Additionally, this molecule directly absorbs UV light (11) and protects biomolecules through direct binding. For example, bound NADPH is known to offset H 2 O 2 -induced inactivation of catalase (13).…”

mentioning

confidence: 99%

“…The corneal epithelium of most mammalian species expresses low molecular weight scavengers of ROS, such as glutathione, ␣-tocopherol, ascorbate, and NADPH (9,10). NADPH is essential for the regeneration of GSH from its oxidized form (GSSG) through the glutathione reductase/peroxidase system, serving as an indirect antioxidant by maintaining the reducing power of GSH (11). NADPH may also function as a direct antioxidant by reducing glutathiyl and tyrosyl radicals generated during oxidative stress (12).…”

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confidence: 99%

Multiple and Additive Functions of ALDH3A1 and ALDH1A1

Lassen¹,

Bateman

Estey³

et al. 2007

Journal of Biological Chemistry

152

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ALDH3A1 (aldehyde dehydrogenase 3A1) is abundant in the mouse cornea but undetectable in the lens, and ALDH1A1 is present at lower (catalytic) levels in the cornea and lens. To test the hypothesis that ALDH3A1 and ALDH1A1 protect the anterior segment of the eye against environmentally induced oxidative damage, Aldh1a1(؊/؊)/Aldh3a1(؊/؊) double knock-out and Aldh1a1(؊/؊) and Aldh3a1(؊/؊) single knock-out mice were evaluated for biochemical changes and cataract formation (lens opacification). The Aldh1a1/Aldh3a1-and Aldh3a1-null mice develop cataracts in the anterior and posterior subcapsular regions as well as punctate opacities in the cortex by 1 month of age. The Aldh1a1-null mice also develop cataracts later in life (6 -9 months of age). One-to three-month-old Aldh-null mice exposed to UVB exhibited accelerated anterior lens subcapsular opacification, which was more pronounced in Aldh3a1(؊/؊) and Aldh3a1(؊/؊)/Aldh1a1(؊/؊) mice compared with Aldh1a1(؊/؊) and wild type animals. Cataract formation was associated with decreased proteasomal activity, increased protein oxidation, increased GSH levels, and increased levels of 4-hydroxy-2-nonenal-and malondialdehyde-protein adducts. In conclusion, these findings support the hypothesis that corneal ALDH3A1 and lens ALDH1A1 protect the eye against cataract formation via nonenzymatic (light filtering) and enzymatic (detoxification) functions.

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Fluorescence Studies of Lens Epithelial Cells and Their Constituents

Cited by 24 publications

References 15 publications

Antioxidant Defenses in the ocular surface

Antioxidant Defenses in the ocular surface

Structural and Functional Modifications of Corneal Crystallin ALDH3A1 by UVB Light

Multiple and Additive Functions of ALDH3A1 and ALDH1A1

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