Extravascular modified lipoproteins: a role in the propagation of diabetic retinopathy in a mouse model of type 1 diabetes

Jeremy Y. Yu, Mei Du, Michael H. Elliott, Mingyuan Wu, Dongxu Fu, Shihe Yang, Arpita Basu, Xiaowu Gu, Jian Xing Ma, Christopher E. Aston, Timothy J. Lyons

Research output: Contribution to journalArticlepeer-review

Abstract

Aims/hypothesis: We aimed to determine whether plasma lipoproteins, after leakage into the retina and modification by glycation and oxidation, contribute to the development of diabetic retinopathy in a mouse model of type 1 diabetes. Methods: To simulate permeation of plasma lipoproteins into retinal tissues, streptozotocin-induced mouse models of diabetes and non-diabetic mice were challenged with intravitreal injection of human ‘highly-oxidised glycated’ low-density lipoprotein (HOG-LDL), native- (N-) LDL, or the vehicle PBS. Retinal histology, electroretinography (ERG) and biochemical markers were assessed over the subsequent 14 days. Results: Intravitreal administration of N-LDL and PBS had no effect on retinal structure or function in either diabetic or non-diabetic animals. In non-diabetic mice, HOG-LDL elicited a transient inflammatory response without altering retinal function, but in diabetic mice it caused severe, progressive retinal injury, with abnormal morphology, ERG changes, vascular leakage, vascular endothelial growth factor overexpression, gliosis, endoplasmic reticulum stress, and propensity to apoptosis. Conclusions/interpretation: Diabetes confers susceptibility to retinal injury imposed by intravitreal injection of modified LDL. The data add to the existing evidence that extravasated, modified plasma lipoproteins contribute to the propagation of diabetic retinopathy. Intravitreal delivery of HOG-LDL simulates a stress known to be present, in addition to hyperglycaemia, in human diabetic retinopathy once blood-retinal barriers are compromised.

Original languageEnglish (US)
Pages (from-to)2026-2035
Number of pages10
JournalDiabetologia
Volume59
Issue number9
DOIs
StatePublished - Sep 1 2016
Externally publishedYes

Keywords

  • Diabetic retinopathy
  • Dyslipidaemia
  • Lipoprotein
  • Oxidised LDL
  • Pathogenesis
  • Vascular complications

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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