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Alfred R. Wegener, Julia E. Kremer, Denise P. Reimnitz, Heike E. Laser-Junga, Roland Müller-Breitenkamp, Ursula Müller-Breitenkamp; Age-related Light Scattering Development in Non-Cataractous Lenses from Diabetic Patients and Possible Biochemical Mechanisms to Explain this Observation. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3049.
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Investigation of age-related non-cataractous light scattering changes in lenses from diabetic patients treated with insulin or non-insulin oral anti-diabetic medication. Demonstration of potential sorbitol-pathway independent mechanisms for light scattering changes in diabetic lenses using an in-vitro assay.
A total of 53 patients were enrolled into the study, 20 male patients (mean age 66,92 ± 10,37 years) and 33 female patients (mean age 68,85 ± 7,22 years). Out of these 24 were insulin treated and 29 patients were treated with oral anti-diabetic medication. Light scattering profiles of all patient lenses were recorded with a Topcon SL-45 Scheimpflug camera on BW film. The images were digitized and evaluated with image analytical software as previously described. For the investigation of glucose-related protein modifications in the lens, crystallin extracts from porcine lenses were incubated with varying concentrations of glucose over 48 h at 37°C and thereafter analyzed with 2D-PAGE and electro-blotting using specific antibodies to detect O-GlcNAc modified proteins.
Light scattering increase in all lens layers of the diabetic patients was significantly higher when compared to an age-matched cohort of non-diabetic healthy patients. In addition higher amounts of light scattering could be detected in layer 4 (anterior cortex) of diabetic patients treated with oral anti-diabetic medication, compared to those on insulin therapy. In-vitro incubation of porcine lens crystallins with varying concentrations of glucose demonstrated that especially βA1, βA4 and γIV crystallins are targets for O-GlcNAc modification, whereas α crystallins were no target for this process.
Clinical data on light scattering in defined lens layers demonstrate that even under anti-diabetic therapy lens optical quality deteriorates more rapidly during aging in diabetic patients. In addition oral anti-diabetic medication is less effective than insulin in maintaining lens transparency in the cortex. The in-vitro assays for O-GlcNAc modification of lens proteins evidence distinct β- and γ-crystallins as targets for this modification which could explain why light scattering in the lens increases even under effective anti-diabetic therapy. This diabetic modification would be completely independent of the sorbitol pathway in the lens.
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