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



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.



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.



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.
Centre for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Science, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland, UK. jeremy.yu@qub.ac.uk.
Jeremy Y
JY
Yu
Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Mei
M
Du
Department of Ophthalmology, Dean A. McGee Eye Institute, Oklahoma City, OK, USA.
Michael H
MH
Elliott
Section of Diabetes and Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Mingyuan
M
Wu
Centre for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Science, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland, UK.
Dongxu
D
Fu
Section of Diabetes and Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Shihe
S
Yang
Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK, USA.
Arpita
A
Basu
Department of Ophthalmology, Dean A. McGee Eye Institute, Oklahoma City, OK, USA.
Xiaowu
X
Gu
Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Jian-Xing
JX
Ma
Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Christopher E
CE
Aston
Centre for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Science, Queen's University Belfast, 97 Lisburn Road, Belfast, BT9 7BL, Northern Ireland, UK. t.lyons@qub.ac.uk.
Timothy J
TJ
Lyons
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000150:complications* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000473:pathology; D003930:Diabetic Retinopathy / Q000097:blood* / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D004596:Electroretinography; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein
Diabetic retinopathy; Dyslipidaemia; Lipoprotein; Oxidised LDL; Pathogenesis; Vascular complications