The data suggest that proliferative DR development may be associated with increased retinal expression of vascular endothelial growth factor, placenta growth factor and transforming growth factor-beta1 that possibly triggers the deposition of small tenascin-C isoforms in the blood vessel walls.
In streptozotocin (STZ)-induced DR rats, TPP (0.4 g/kg) treatment restored electrophysiology indexes and retinal ultrastructures, reduced serum IL-6 and TNF-α levels, decreased VEGF and bFGF expression in retinal tissues, and improved haemorheology indexes.
Our results suggest that 1) IGFBP-3 inhibits the endothelial nitric oxide synthase (eNOS) and protein kinase C zeta (PKCzeta) pathway, which in turn inhibits VEGF production, and 2) that eNOS plays a role in activating PKCzeta to increase VEGF levels in diabetic retinopathy.
Using ocular clinical samples and animal disease models, we elucidated molecular mechanisms in which tissue RAS excites the expression of vascular endothelial growth factor (VEGF)-A responsible for retinal inflammation and angiogenesis, the two major pathological events in diabetic retinopathy (DR).
In vivo, in parallel with the increase in PEDF we observed a decrease in VEGF levels in injected compared with noninjected eyes and a significant effect on two hallmarks of DR: reduction of glucose transport (by glucose transporter GLUT1), and reduction of inflammation by decreased reactivity of microglia.
Further to assess the therapeutic efficacy of diabetic retinopathy, we showed Chit-DC-VB12-Scu down-regulated central retinal artery resistivity index and the expression of angiogenesis proteins (VEGF, VEGFR2, and vWF) of retinas in type II diabetic rats.
Hyperglycemia invoke number of pathways resulting in development of diabetic retinopathy (DR), including protein kinase C activation, increased expression of VEGF, advanced glycation end product (AGEs) formation and activation of polyol pathway, among which the pathophysiology of aldose reductase (ALR2) of the polyol pathway is evident by more than a decade of research.
Our previous studies demonstrated that G protein-coupled receptor 91(GPR91) participated in the regulation of vascular endothelial growth factor (VEGF) secretion in DR.
Overall, serum VEGF levels were significantly higher in DR patients (SMD: 0.74, 95% CI: 0.44-1.03) than those in NDR patients, while plasma VEGF levels were not in the comparison (SMD: 0.40, 95% CI: -0.13-0.92).
Elevated expression of photoreceptor-secreted RBP3 may have a role in protection against the progression of DR due to hyperglycemia by inhibiting glucose uptake via GLUT1 and decreasing the expression of inflammatory cytokines and VEGF.
The aim of the present study is to investigate the exact role and mechanism of lncRNA MALAT1 (MALAT1) in the progress of DR. Oxygen-induced retinopathy (OIR) mouse model and high glucose (HG)-stimulated human retinal microvascular endothelial cells (HRMECs) were employed to mimic the pathological statues of DR. qRT-PCR or western blot results showed that MALAT1, VEGFA and HIF-1α levels were increased in DR retinal tissues and HG-stimulated HRMECs, whereas the expression of miR-203a-3p was decreased.
VEGF levels in tears were significantly higher amongst diabetic patients with DR compared to those without DR and were significantly associated with the severity of DR.
In conclusion, IGF-I participates in the pathophysiology of diabetic retinopathy by inducing retinal VEGF expression via PI-3K/Akt, HIF-1alpha, NF-kappaB, and secondarily, JNK/AP-1 activation.
The development of early DR was confirmed by the expression profiles of ZO-1 and VEGFA in the retina as well as the compromised integrity of the inner BRB.
Therefore, it was concluded that lncRNA MEG3 overexpression may inhibit the development of diabetic retinopathy by inhibiting TGF-β1 and VEGF expression.
The aim of the present study was to investigate the inhibitory effect of fenofibrate on metabolic memory (via the regulation of SIRT1), and inflammatory responses in cell and animal models of diabetic retinopathy (DR).
It was suggested that further exploration of the MCP-1/CCR2 axis association between clinical stages of DR and expression levels of inflammatory and angiogenic cytokines and chemokines, principally the MCP-1 might lead to potential therapies aiming at neutralizing antibodies and viral vectors.
The mean plasma PEDF level in patients with PDR (7.69+/-6.14 microg/ml; mean+/-standard error) was significantly higher than that of mild-to-moderate nonproliferative diabetic retinopathy (5.07+/-4.37 microg/ml, p=0.02).