Advanced glycation end (AGE) product modification of laminin downregulates Kir4.1 in retinal Müller cells

PloS One
Kayla ThompsonAshay Bhatwadekar

Abstract

Diabetic retinopathy (DR) is a major cause of adult blindness. Retinal Müller cells maintain water homeostasis and potassium concentration via inwardly rectifying Kir4.1 channels. Accumulation of advanced glycation end products (AGEs) is a major pathologic event in DR. While diabetes leads to a decrease in the Kir4.1 channels, it remains unknown whether AGEs-linked to the basement membrane (BM) affect normal Kir4.1 channels. For this study, we hypothesized that AGE-modification of laminin is detrimental to Kir4.1 channels, therefore, disrupting Müller cell function. The AGE-modified laminin-coated substrates were prepared by incubating Petri-dishes with laminin and methylglyoxal for seven days. The rat Müller cells (rMC-1) were propagated on AGE-modified laminin, and Kir4.1 expression and function were evaluated. Quantification of AGEs using ELISA revealed a dose-dependent increase in methylglyoxal-hydro-imidazolone adducts. The rMC-1 propagated on AGE-modified laminin demonstrated a decrease in Kir4.1 levels in immunofluorescence and western blot studies and a decrease in the Kir4.1 channel function. Kir4.1 decrease on AGE-modified laminin resulted in a disorganization of an actin cytoskeleton and disruption of α-dystroglycan-...Continue Reading

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Citations

Sep 29, 2018·Current Protein & Peptide Science·Nikhil Shri SahajpalSubheet Kumar Jain
May 3, 2019·Investigative Ophthalmology & Visual Science·Qianyi LuoAshay D Bhatwadekar
Feb 13, 2020·Investigative Ophthalmology & Visual Science·Mirella Telles Salgueiro BarboniJan Kremers
Jul 3, 2020·Journal of Cellular and Molecular Medicine·Tangting ChenLiqun Wang
Feb 26, 2020·European Psychiatry : the Journal of the Association of European Psychiatrists·Gerwyn MorrisBasant K Puri
Jan 21, 2021·Nature Reviews. Endocrinology·David A AntonettiAlan W Stitt
Aug 11, 2021·Experimental and Therapeutic Medicine·Xiaoyu LiXiang Ren

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Methods Mentioned

BETA
ELISA
confocal microscopy
transfection

Software Mentioned

Quantity One
Zen11
Icy
GraphPad
Graph Pad - Prizm
ImageJ

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