Early Diabetes Induces Changes in Mitochondrial Physiology of Inner Retinal Neurons. (15th May 2019)

• Record Type: Journal Article
• Authors: Haider, Syeda Zehra; Sadanandan, Nidish P.; Joshi, Preeti G.; Mehta, Bhupesh
• Is Part Of: Neuroscience. Volume 406(2019)
• Page Start: 140
• Page End: 149
• Publication Date: 2019-05-15
• Subjects: ANOVA analysis of variance -- ARVO Association for Research in Vision and Ophthalmology -- CCCP carbonyl cyanide m-chlorophenyl hydrazine -- EMEM eagle's minimal essential medium -- ERG glycosylated hemoglobin -- ER endoplasmic reticulum -- HbA1C glycosylated hemoglobin -- HBSS Hanks' balanced salt solution -- H2DCFDA 2', 7'-dichlorodihydrofluorescein diacetate -- HEPES 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid -- HGC high glucose medium condition -- H2O2 hydrogen peroxide -- INL inner nuclear layer -- OP oscillatory potential -- PR photoreceptor -- ROS reactive oxygen species -- SOD superoxide dismutase -- STZ streptozotocin -- TMRE tetramethylrhodamine methyl ester; diabetes -- retina -- electroretinogram -- mitochondria -- calcium homeostasis -- reactive oxygen species; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2019.02.026
• Languages: English
• ISSNs: 0306-4522

Abstract

Abstract: Diabetic retinopathy, a leading cause of vision loss, was considered as a solely vascular disorder but some recent studies suggest that retinal neurons may be affected much before the appearance of vascular lesions. However, the cellular processes involved in diabetes-induced degeneration of retinal neurons are poorly understood. Calcium (Ca 2+ ) signaling plays a key role in normal functioning of neurons, and its dysregulation may lead to degeneration of neurons. Mitochondria are crucial components involved in the regulation of intracellular Ca 2+ signaling. In this study, we have investigated the effects of diabetes on Ca 2+ signaling in retinal neurons. The study was performed in rat retinal neurons cultured in high glucose condition (HGC) for 7–14 days and in acutely prepared retinal slices isolated from diabetic rats. When Ca 2+ influx was induced by depolarization of neurons with 60 mM KCl in HGC neurons, the Ca 2+ rise was sustained for a much longer duration as compared to controls, suggesting perturbation of Ca 2+ buffering. In addition, HGC neurons also showed notably enhanced Ca 2+ load in the mitochondria, which was accompanied by depolarization of mitochondrial membrane and enhanced reactive oxygen species formation. Similar results were obtained in acutely prepared retinal slices from control and diabetic rats. The depolarization of mitochondrial membrane was more pronounced in the neurons of the inner nuclear layer of diabetic rats. The physiological changes in mitochondria were observed as early as 9 weeks post diabetes induction. Thus, we report here that the intracellular Ca 2+ signaling and mitochondrial function in retinal neurons are altered at an early stage of diabetes. Highlights: Neuronal dysfunction in retina appears at an early stage of diabetes. Type 1 diabetes increases the depolarization of mitochondrial membrane potential. Diabetes causes decrease in a-wave and b-wave amplitudes in rat scotopic electroretinogram.