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Aldo-keto reductases in the eye.

Huang SP, Palla S, Ruzycki P, Varma RA, Harter T, Reddy GB, Petrash JM - J Ophthalmol (2010)

Bottom Line: Aldose reductase (AKR1B1) is an NADPH-dependent aldo-keto reductase best known as the rate-limiting enzyme of the polyol pathway.Some human tissues contain AKR1B1 as well as AKR1B10, a closely related member of the aldo-keto reductase gene superfamily.These results indicate that AKR1B1 and AKR1B10 may have different functional properties in the lens and suggest that AKR1B10 does not contribute to the pathogenesis of diabetic cataract in humans.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.

ABSTRACT
Aldose reductase (AKR1B1) is an NADPH-dependent aldo-keto reductase best known as the rate-limiting enzyme of the polyol pathway. Accelerated glucose metabolism through this pathway has been implicated in diabetic cataract and retinopathy. Some human tissues contain AKR1B1 as well as AKR1B10, a closely related member of the aldo-keto reductase gene superfamily. This opens the possibility that AKR1B10 may also contribute to diabetic complications. The goal of the current study was to characterize the expression profiles of AKR1B1 and AKR1B10 in the human eye. Using quantitative reverse transcriptase-PCR and immunohistochemical staining, we observed expression of both AKR genes in cornea, iris, ciliary body, lens, and retina. Expression of AKR1B1 was the highest in lens and retina, whereas AKR1B10 was the highest in cornea. Lenses from transgenic mice designed for overexpression of AKR1B10 were not significantly different from nontransgenic controls, although a significant number developed a focal defect in the anterior lens epithelium following 6 months of experimentally induced diabetes. However, lenses from AKR1B10 mice remained largely transparent following longterm diabetes. These results indicate that AKR1B1 and AKR1B10 may have different functional properties in the lens and suggest that AKR1B10 does not contribute to the pathogenesis of diabetic cataract in humans.

No MeSH data available.


Related in: MedlinePlus

Lens defect in AKR1B10 lens after long-term diabetes. (a) Brightfield microscopy of transgenic lens demonstrating light scattering defect (arrow). (b) AKR1B10 transgenic lens showing defect at the anterior aspect of the lens (arrow). (c) Magnification of the boxed area from panel (b). (d) Lens from nontransgenic control with equivalent duration of diabetes. Panels (b)–(d) are from toluidine blue-stained lenses.
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fig4: Lens defect in AKR1B10 lens after long-term diabetes. (a) Brightfield microscopy of transgenic lens demonstrating light scattering defect (arrow). (b) AKR1B10 transgenic lens showing defect at the anterior aspect of the lens (arrow). (c) Magnification of the boxed area from panel (b). (d) Lens from nontransgenic control with equivalent duration of diabetes. Panels (b)–(d) are from toluidine blue-stained lenses.

Mentions: We induced experimental diabetes in our transgenic mice to determine if over-expression of AKR1B10 influences the susceptibility of the mouse lens to cataracts. Both transgenic and nontransgenic animals with and without experimental diabetes were monitored for up to six months for the appearance of lens opacities. In all cases, the lenses remained essentially clear and developed only minor focal areas of light scattering in the lens nucleus, typical of the normal aging mouse lens [16]. A refractive abnormality localized on the anterior epithelium was observed in 50% (3 of 6) of the AKR1B10 mice with diabetes. This defect gave rise to light scattering when viewed through a slit lamp ophthalmoscope or after dissection and brightfield illumination (Figure 4). Histological examination showed that this abnormality was associated with a localized disorganization of epithelial cells, formation of large vacuoles, and disrupted contact between epithelial cells and the lens capsule. This defect was not observed in age-matched nontransgenic controls with equivalent duration of experimental diabetes (n = 4) or in nondiabetic transgenic controls (n > 6). The epithelial defect we observed is fundamentally different from cortical opacities that characterize the majority of diabetic cataracts.


Aldo-keto reductases in the eye.

Huang SP, Palla S, Ruzycki P, Varma RA, Harter T, Reddy GB, Petrash JM - J Ophthalmol (2010)

Lens defect in AKR1B10 lens after long-term diabetes. (a) Brightfield microscopy of transgenic lens demonstrating light scattering defect (arrow). (b) AKR1B10 transgenic lens showing defect at the anterior aspect of the lens (arrow). (c) Magnification of the boxed area from panel (b). (d) Lens from nontransgenic control with equivalent duration of diabetes. Panels (b)–(d) are from toluidine blue-stained lenses.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2902055&req=5

fig4: Lens defect in AKR1B10 lens after long-term diabetes. (a) Brightfield microscopy of transgenic lens demonstrating light scattering defect (arrow). (b) AKR1B10 transgenic lens showing defect at the anterior aspect of the lens (arrow). (c) Magnification of the boxed area from panel (b). (d) Lens from nontransgenic control with equivalent duration of diabetes. Panels (b)–(d) are from toluidine blue-stained lenses.
Mentions: We induced experimental diabetes in our transgenic mice to determine if over-expression of AKR1B10 influences the susceptibility of the mouse lens to cataracts. Both transgenic and nontransgenic animals with and without experimental diabetes were monitored for up to six months for the appearance of lens opacities. In all cases, the lenses remained essentially clear and developed only minor focal areas of light scattering in the lens nucleus, typical of the normal aging mouse lens [16]. A refractive abnormality localized on the anterior epithelium was observed in 50% (3 of 6) of the AKR1B10 mice with diabetes. This defect gave rise to light scattering when viewed through a slit lamp ophthalmoscope or after dissection and brightfield illumination (Figure 4). Histological examination showed that this abnormality was associated with a localized disorganization of epithelial cells, formation of large vacuoles, and disrupted contact between epithelial cells and the lens capsule. This defect was not observed in age-matched nontransgenic controls with equivalent duration of experimental diabetes (n = 4) or in nondiabetic transgenic controls (n > 6). The epithelial defect we observed is fundamentally different from cortical opacities that characterize the majority of diabetic cataracts.

Bottom Line: Aldose reductase (AKR1B1) is an NADPH-dependent aldo-keto reductase best known as the rate-limiting enzyme of the polyol pathway.Some human tissues contain AKR1B1 as well as AKR1B10, a closely related member of the aldo-keto reductase gene superfamily.These results indicate that AKR1B1 and AKR1B10 may have different functional properties in the lens and suggest that AKR1B10 does not contribute to the pathogenesis of diabetic cataract in humans.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.

ABSTRACT
Aldose reductase (AKR1B1) is an NADPH-dependent aldo-keto reductase best known as the rate-limiting enzyme of the polyol pathway. Accelerated glucose metabolism through this pathway has been implicated in diabetic cataract and retinopathy. Some human tissues contain AKR1B1 as well as AKR1B10, a closely related member of the aldo-keto reductase gene superfamily. This opens the possibility that AKR1B10 may also contribute to diabetic complications. The goal of the current study was to characterize the expression profiles of AKR1B1 and AKR1B10 in the human eye. Using quantitative reverse transcriptase-PCR and immunohistochemical staining, we observed expression of both AKR genes in cornea, iris, ciliary body, lens, and retina. Expression of AKR1B1 was the highest in lens and retina, whereas AKR1B10 was the highest in cornea. Lenses from transgenic mice designed for overexpression of AKR1B10 were not significantly different from nontransgenic controls, although a significant number developed a focal defect in the anterior lens epithelium following 6 months of experimentally induced diabetes. However, lenses from AKR1B10 mice remained largely transparent following longterm diabetes. These results indicate that AKR1B1 and AKR1B10 may have different functional properties in the lens and suggest that AKR1B10 does not contribute to the pathogenesis of diabetic cataract in humans.

No MeSH data available.


Related in: MedlinePlus