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P. E. Fort, M. K. Losiewicz, W. M. Freeman, T. W. Gardner; Retinal Protein Regulation During Diabetes: Crystallin Up-Regulation, a New Piece of the Puzzle. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1324.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the perturbations of the retinal proteome during diabetes. The retina has a high metabolic rate and requires continual protein synthesis to maintain cellular integrity and visual processes. We showed previously that global retinal protein synthesis is rapidly impaired during diabetes.
Transcriptional profiles were assessed using whole genome Codelink microarrays and mRNA expression levels were confirmed using real-time RT-PCR. DIGE 2D-gels method was used to characterize the proteome modifications in the retinas of diabetic rats compared to their age-matched controls. Western-blot and immunohistochemistry analysis, respectively, were used to determine levels of protein expression and cellular localization. Effects of local and systemic insulin administration were also assessed using western-blot methods.
Transcriptional and translational levels of expression of numerous proteins were increased dramatically in diabetic animals, concurrent with decreased global retinal protein synthesis. Microarray analysis of retinal mRNA expression demonstrated dramatic increases of the alpha-, beta- and gamma-crystallins transcripts. Use of proteomic and western-blot approaches confirmed the increased expression of the crystallin proteins. Immunohistochemical studies showed that some of those proteins had a very specific localization pattern correlated with the retinal neuronal layers most affected in diabetes. Local and systemic insulin administration partially restored the protein synthetic alterations.
This study shows for the first time that the diabetes-induced disruption of retinal protein synthesis is a targeted phenomenon. Up-regulation of the retinal crystallins may involve their chaperone role for damaged proteins or a possible inflammation component of diabetes. Characterization of this phenomenon may lead to new potential therapeutic approaches for the treatment of diabetic retinopathy.
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