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Retina

Diabetes-Induced Inflammation and Vascular Alterations in the Goto–Kakizaki Rat Retina

, , &
Pages 965-974 | Received 20 May 2019, Accepted 30 Dec 2019, Published online: 20 Jan 2020
 

ABSTRACT

Purpose

Diabetic retinopathy is characterized by multiple microcirculatory dysfunctions and angiogenesis resulting from hyperglycemia, oxidative stress, and inflammation. In this study, the retina and retinal pigmented epithelium of non-insulin-dependent diabetic Goto–Kakizaki (GK) rats were examined to detect microvascular alterations, gliosis, macrophage infiltration, lipid deposits, and fibrosis. Emphasis was given to the distribution of kinin B1 receptor (B1R) and vascular endothelial growth factor (VEGF), two major factors in inflammation and angiogenesis.

Materials and methods

30-week-old male GK rats and age-matched Wistar rats were used. The retinal vascular bed was examined using ADPase staining. The level of lipid accumulation was graded using triglyceride staining with Oil red O. Macrophage and retinal microglia activation, as well as other markers, were revealed by immunohistochemistry and studied with confocal laser scanning microscopy.

Results

Abundant lipid deposits were observed in the Bruch’s membrane of GK rats. Immunohistochemistry and quantitative analysis showed significantly higher B1R, VEGF, Iba1 (microglia), CD11 (macrophages), fibronectin, and collagen I labeling in the diabetic retina. B1R immunolabeling was detected in the vascular layers of the GK retina. A strong VEGF staining within different retinal cell processes was detected and a pattern of GFAP staining suggested strong Müller cells/astrocytes reactivity. Microgliosis was apparent in the GK retina. A greater tortuosity of the retinal microvessels (an index of endothelial dysfunction) and their increased number were also observed in GK retinas.

Conclusions

Data suggest retinal vascular bed alterations in spontaneous type 2 diabetic retinas at 30 weeks. Lipid and collagen accumulation in the retina and choroid, in addition to retinal upregulation of VEGF and B1R, microgliosis, and Müller cell reactivity, may contribute to vascular alterations and inflammatory processes.

Acknowledgments

The authors greatly appreciate the technical assistance of Tamara Boutin, Frédéric Huppé-Gourgues and Florence Dotigny for the immunohistochemistry experiments.

Conflict of interest

Authors declare no conflict of interest.

Additional information

Funding

This work was supported by a grant from the Canadian Institutes of Health Research (MOP-125962) to EV and RC, and from Le Fonds de recherche du Québec-Santé (FRQS), Vision Health Research Network (networking program) to EV, RC. SH was recipient of a scholarship from the GRUM- Université de Montréal.

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