Early cellular and molecular changes induced by diabetes in the retina

Lorenzi, Mara; Gerhardinger, Chiara

doi:10.1007/s001250100544

Cited by 190 publications

(143 citation statements)

References 65 publications

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“…Apoptosis could play a role in early pericyte dropout of diabetic retinopathy [9]. Mechanisms proposed to account for this phenomenon include rapid fluctuations of blood glucose, increased Bax expression during hyperglycaemia, aldose-reductase hyperactivity, increased AGE production and nuclear factor-kappa B activation [9,10]. Our results confirm that high glucose increases pericyte apoptosis and suggest that PKC inhibition could further amplify it.…”

Section: Discussionsupporting

confidence: 71%

“…LY379196 increased the percentage of resting cells (G0/G1), whereas PKC stimulation markedly increased actively replicating ones (S and G2/M), confirming a major role for PKC in pericyte progression along the cell cycle. Apoptosis could play a role in early pericyte dropout of diabetic retinopathy [9]. Mechanisms proposed to account for this phenomenon include rapid fluctuations of blood glucose, increased Bax expression during hyperglycaemia, aldose-reductase hyperactivity, increased AGE production and nuclear factor-kappa B activation [9,10].…”

Section: Discussionmentioning

confidence: 99%

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Effects of protein kinase C inhibition and activation on proliferation and apoptosis of bovine retinal pericytes

et al. 2003

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Aims/hypothesis. Drop-out of capillary pericytes occurs early and selectively in diabetic retinopathy. High glucose concentrations decrease replication and increase apoptosis of cultured pericytes. Since glucose activates protein kinase C, we investigated the effects of modulating this intracellular mediator on replication, cell cycle and apoptosis of cultured bovine retinal pericytes. Methods. Pericytes cultured in 5.6 or 28 mmol/l glucose were exposed to a protein kinase C activator (phorbol 12-myristate 13-acetate) and/or a selective inhibitor of its β2 isoform (LY379196). Cells were counted after 7 days. Proliferation by the tetrazolium to formazan assay and DNA synthesis by 5-bromo-2′-deoxyuridine incorporation were measured at day 4. Cell cycle by flow cytometry and apoptosis by ELISA were assessed at day 2. Results. High glucose reduced pericyte replication and increased apoptosis. Protein kinase C activation increased proliferation, while inhibition of its β2 isoform decreased it. Cell cycle was accelerated by protein kinase C activation and delayed by inhibition. Apoptosis was enhanced by protein kinase C inhibition and reduced by activation. Conclusions/interpretation. Protein kinase C inhibition amplifies the anti-proliferative and pro-apoptotic effects of high glucose on cultured pericytes, whereas stimulation reduces apoptosis and promotes proliferation both in physiological glucose and high glucose. Protein kinase C inhibition, proposed for the treatment of diabetic macular edema and proliferative retinopathy, might accelerate pericyte dropout in earlier stages when these cells are still present in retinal capillaries. [Diabetologia (2003) 46:416-419]

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Effects of protein kinase C inhibition and activation on proliferation and apoptosis of bovine retinal pericytes

et al. 2003

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“…Neurodegeneration is an early event in the pathogenesis of diabetic retinopathy, antedating and participating in the microcirculatory abnormalities that occur in the condition [2,3,24]. Neuroretinal damage produces functional abnormalities such as colour vision defects, reduced contrast sensitivity and abnormalities in dark adaptation.…”

Section: Discussionmentioning

confidence: 99%

“…However, before any microcirculatory abnormalities can be detected, retinal neurodegeneration is already present [1][2][3][4]. In fact, we have detected apoptosis and glial activation, two characteristic features of retinal neurodegeneration, in retinas from diabetic donors, which were free of microcirculatory abnormalities in ophthalmoscopic examinations performed in the 2 years preceding death [5,6].…”

Section: Introductionmentioning

confidence: 89%

Interphotoreceptor retinoid-binding protein (IRBP) is downregulated at early stages of diabetic retinopathy

et al. 2009

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Aims/hypothesis Interphotoreceptor retinoid-binding protein (IRBP) plays a major role in the visual cycle and is essential to the maintenance of photoreceptors. The aim of this study was to determine whether a decrease in IRBP production exists in the early stages of diabetic retinopathy. Methods Vitreous samples from diabetic patients with proliferative and non-proliferative diabetic retinopathy (PDR, NPDR), and from non-diabetic patients with macular hole (control group) were selected for IRBP quantitative assessment by proteomic analysis (fluorescence-based difference gel electrophoresis) and western blot. Human post mortem eyes (n=16) from diabetic donors without clinically detectable retinopathy and from non-diabetic donors (n=16) were used to determine IRBP (also known as RBP3) mRNA levels (RT-PCR) and protein content (western blot and confocal microscopy). Retinal neurodegeneration was assessed by measuring glial fibrillar acidic protein (GFAP) and the apoptotic rate. Y79 human retinoblastoma cells were used to test the effects of glucose, TNF-α and IL-1β on IRBP expression and IRBP levels. Results Intravitreous IRBP concentration was significantly lower in PDR

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“…We believe that the conclusion could have been different, if they had investigated these pathological processes in the tissue affected by diabetes, i.e. in the retina [4].…”

mentioning

confidence: 98%

?to: Gardiner TA, Anderson HR, Degenhardt T et al. (2003) Prevention of retinal capillary basement membrane thickening in diabetic dogs by a non-steroidal anti-inflammatory drug. Diabetologia 46:1269?1275

Biswas

Faria

2004

Diabetologia

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Early cellular and molecular changes induced by diabetes in the retina

Cited by 190 publications

References 65 publications

Effects of protein kinase C inhibition and activation on proliferation and apoptosis of bovine retinal pericytes

Effects of protein kinase C inhibition and activation on proliferation and apoptosis of bovine retinal pericytes

Interphotoreceptor retinoid-binding protein (IRBP) is downregulated at early stages of diabetic retinopathy

?to: Gardiner TA, Anderson HR, Degenhardt T et al. (2003) Prevention of retinal capillary basement membrane thickening in diabetic dogs by a non-steroidal anti-inflammatory drug. Diabetologia 46:1269?1275

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