Long-term exposure to high glucose increases the content of several exocytotic proteins and of vesicular GABA transporter in cultured retinal neural cells

Involvement of Autophagic Pathway in the Progression of Retinal Degeneration in a Mouse Model of Diabetes

“…Down-regulation of photoreceptor presynaptic proteins has been observed in other rodent models of diabetes (Park et al, 2003 ; Ozawa et al, 2011 ; Hombrebueno et al, 2014 ) as well as in patients with mild DR (Varga et al, 2015 ). Multiple evidence from cultured retinal explants suggests that high glucose exposure is sufficient to cause altered expression of key synaptic components such as vesicular GABA transporter (Baptista et al, 2015 ), purinergic receptors (Vindeirinho et al, 2013 ) and extracellular ATP levels (Costa et al, 2009 ), thus making the synaptic layers of the retina particularly prone to alterations occurring in early phases of DR. We therefore propose that the synaptic contacts in the outer retina undergo increased autophagy in response to diabetes. Up-regulation of autophagy occurs within the same time frame of outer retina damage and thus possibly represents the process leading to photoreceptor death in the early phase of DR.…”

Melanocortin receptor agonists MCR1‐5 protect photoreceptors from high‐glucose damage and restore antioxidant enzymes in primary retinal cell culture

“…Western blotting was performed on retinal cell lysates obtained following the protocol described by Baptista et al, [10]. Briefly, cells were washed with ice-cold phosphate-buffered saline (PBS, in mM: 137 NaCl, 2.7 KCl, 10 Na 2 HPO 4 , 1.8 KH 2 PO 4 , pH 7.4, at 4°C) and lysed with RIPA buffer (50 mM Tris-HCl, pH 7.4, 150 mM NaCl, 5 mM EDTA, 1% Triton X-100, 0.5% DOC, 0.1% SDS, 1 mM DTT) supplemented with complete miniprotease inhibitor cocktail tablets and phosphatase inhibitors (10 mM NaF and 1 mM Na 3 VO 4 ).…”

“…Several cell types are included on retina for example amacrine cells, M € uller cells, ganglion cells and photoreceptors among others. It has been demonstrated that retinal photoreceptors are particularly vulnerable to local highglucose concentrations [10] and oxidative stress is a risk factor for diabetic retinopathy development [11], and retinal photoreceptor alterations may play an important role in the progression of diabetic retinopathy [12].…”

Elevation in Circulating Soluble CD40 Ligand Concentrations in Type 2 Diabetic Retinopathy and Association with its Severity

“…DWR and DR patients were matched according to age, BMI, and lipid profile, thereby ruling out the contribution of obesity [11] or lipotoxicity [33,34] to DR. In addition, significant differences between both T2DM patient groups were seen in the age of onset and duration of diabetes, and HbA1c, confirming the role of long exposure to hyperglycemia and poor glycemic control to DR [24,[34][35][36]. This appears to influence DR severity, as higher sCD40L levels were seen in PDR more so than NPDR patients, which is likely attributed to hyperglycemia and insulin resistance (HOMA-IR) [18].…”