Purchase this article with an account.
Ashay D Bhatwadekar, Osama Mufti, Qianyi Luo; Circadian Arrhythmia Alters Retinal Kir4.1 Expression. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5205.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The Müller cell, a major glia of the retina maintains K+ balance through inwardly rectifying Kir4.1 channels. Studies in our laboratory suggest that the Kir4.1 channels exhibit a diurnal rhythm. Clock-controlled genes regulate about 10% of the transcriptome; therefore, improper regulation of circadian rhythms likely contributes to disorders that include obesity, metabolic syndrome, and type 2 diabetes (T2D). However, it remains unknown whether circadian rhythm disruption (CRD) affects retinal Kir4.1 expression, therefore the purpose of this investigation is to determine the influence of CRD on Kir4.1 regulation and Müller cell dysfunction
The T2D mice (db/db) and control mice (db/m) were maintained under regular light-dark (LD) conditions or exposed to a constant dark to induce the CRD in circadian cabinets. The locomotor activity was evaluated using the Clock-Lab software. After two weeks, the plasma levels of insulin and leptin were evaluated. The retinal expression of clock genes Per2, Bmal and Kir4.1 was determined.
The db/m mice in the LD group exhibited a locomotor activity consistent with the nocturnal nature of animals. However, the movements of the diabetic mice were sporadic. The CRD altered the normal locomotor behavior of both db/m and db/db mice with a profound decrease in the mean onset of activity (p<0.05). In db/m mice, CRD lead to hyperinsulinemia and hyperleptinemia with a decrease in the levels of retinal clock genes, Per2 (1.8-fold p<0.05) and Bmal1 (1.7-fold; p<0.05). The db/db mice demonstrated a greater reduction of clock genes. The Kir4.1 expression exhibited a diurnal rhythm in the retina of db/m mice, however, the diabetic mice were devoid of this rhythm. CRD resulted in disruption of diurnal rhythm in both db/m and db/db animals.
Our studies demonstrate that CRD leads to a decrease in Kir4.1 expression, which may result in Müller cell dysfunction. Thus, circadian rhythm regulation is critical for protection from Müller cell dysfunction in diabetes.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
This PDF is available to Subscribers Only