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Metabolic memory and diabetic retinopathy: role of inflammatory mediators in retinal pericytes.

Abstract：

:Diabetic retinopathy shares many characteristics features of a low grade chronic inflammatory disease. Its progression resists arrest when good metabolic control is re-established after a period of poor metabolic control, suggesting a 'metabolic memory' phenomenon. The aim of this study is to investigate the effect of reversal of high glucose to normal glucose on the inflammatory mediators in pericytes, the site of histopathology in diabetic retinopathy. Bovine retinal pericytes were incubated in high glucose (20 mM) for 2 days followed by normal glucose (5 mM) for 4 days (2 --> 4), or in high glucose for 4 days followed by normal glucose for 4 days (4 --> 4) or 8 days (4 --> 8). Pericytes incubated in continuous normal or high glucose for 2-12 days served as controls. Continuous high glucose exposure for 2-12 days significantly elevated gene expressions and protein concentrations of IL-1 beta, NF-kB, VEGF, TNF-alpha, TGF-beta and ICAM-1 in retinal pericytes. Four days of normal glucose that followed 2 days of high glucose (2 --> 4) had marginal, but significant, beneficial effect on the increases in these inflammatory mediators. Four days of normal glucose in 4 --> 4 group failed to reverse increases in inflammatory mediators and cell apoptosis remained elevated, but addition of dexamethasone during normal glucose exposure ameliorated such increases. However, when normal glucose exposure, after 4 days of high glucose was extended to 8 days (4 --> 8), increases in these mediators were significantly decreased. Hyperglycemia-induced elevations in inflammatory mediators in retinal microvascular cells resist reversal after re-institution of normal glucose conditions. Both, the duration of the initial exposure to high glucose, and normal glucose that follows high glucose, are critical in determining the outcome of the alterations in the inflammatory mediators.

journal_name

Exp Eye Res

journal_title

Experimental eye research

authors

Kowluru RA,Zhong Q,Kanwar M

doi

10.1016/j.exer.2010.02.006

subject

Has Abstract

pub_date

2010-05-01 00:00:00

pages

617-23

issue

eissn

0014-4835

issn

1096-0007

pii

S0014-4835(10)00051-5

journal_volume

pub_type

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Metabolic memory and diabetic retinopathy: role of inflammatory mediators in retinal pericytes.