Kir4.1 diabetic retinopathy rat

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...

Purpose: Diabetic patients often are affected by vision problems. We previously identified diabetic retinopathy (DR) as a disease of clock gene dysregulation. TNF-α, a proinflammatory cytokine, is known to be elevated in DR. Müller cells maintain retinal water homeostasis and K+ concentration via Kir4.1 channels. Notably, Kir4.1 expression is reduced in diabetes; however, the interplay of TNF-α, Kir4.1, and clock genes in Müller cells remains unknown. We hypothesize that the Kir4...

PURPOSE: A predominant function of Müller cells is to regulate glutamate levels, but it is compromised in diabetic retinopathy (DR). The present study was performed to determine the role of pigment epithelium-derived factor (PEDF) in glutamate uptake in retinal Müller cells in high-glucose conditions. METHODS: The levels of Kir4.1, PEDF, and GLAST in retinal Müller cells in high-glucose conditions were analyzed by Western blot analysis and real-time RT-PCR, and a glutamate uptake assay was undertaken to investigate the activity of GLAST...

AIMS/HYPOTHESIS: Methylglyoxal (MG) is an important precursor for AGEs. Normally, MG is detoxified by the glyoxalase (GLO) enzyme system (including component enzymes GLO1 and GLO2). Enhanced glycolytic metabolism in many cells during diabetes may overpower detoxification capacity and lead to AGE-related pathology. Using a transgenic rat model that overexpresses GLO1, we investigated if this enzyme can inhibit retinal AGE formation and prevent key lesions of diabetic retinopathy. METHODS: Transgenic rats were developed by overexpression of full length GLO1...

This study examined aquaporin 4 (AQP4) and Kir4.1 (a potassium channel subunit) in normal and diabetic adult Sprague-Dawley rats, and determined the effect of minocycline treatment. Retinal expression of the AQP4 and Kir4.1 genes was examined using double immuno fluorescence, Western blot analysis, and real-time reverse transcription-polymerase chain reaction. Retinal levels of vascular endothelial growth factor (VEGF), ionized calcium-binding adaptor molecule (Iba)-1 and interleukin (IL)-1β were also ascertained...

PURPOSE: Recent evidence suggests that neuroglial dysfunction and degeneration contributes to the etiology and progression of diabetic retinopathy. Advanced lipoxidation end products (ALEs) have been implicated in the pathology of various diseases, including diabetes and several neurodegenerative disorders. The purpose of the present study was to investigate the possible link between the accumulation of ALEs and neuroretinal changes in diabetic retinopathy. METHODS: Retinal sections obtained from diabetic rats and age-matched controls were processed for immunohistochemistry using antibodies against several well defined ALEs...

AIMS/HYPOTHESIS: The impact of AGEs and advanced lipoxidation end-products (ALEs) on neuronal and Müller glial dysfunction in the diabetic retina is not well understood. We therefore sought to identify dysfunction of the retinal Müller glia during diabetes and to determine whether inhibition of AGEs/ALEs can prevent it. METHODS: Sprague-Dawley rats were divided into three groups: (1) non-diabetic; (2) untreated streptozotocin-induced diabetic; and (3) diabetic treated with the AGE/ALE inhibitor pyridoxamine for the duration of diabetes...

The development of edema in the diabetic retina may be caused by vascular leakage and glial cell swelling. To determine whether diabetic retinopathy alters the swelling characteristics of retinal glial cells and changes the properties of the glial membrane K+ conductance, isolated retinas and glial cells of rats were investigated at 4 and 6 months of chemical diabetes. After 6 months of hyperglycemia, application of a hypotonic solution to retinal slices induced swelling of glial cell bodies, a response not observed in control retinas...