Abstract
Purpose :
Spontaneously Diabetic Torii (SDT) fatty rat is a novel animal model for obesity and type 2 diabetes. SDT fatty rat develops hyperglycemia, dyslipidemia and other diabetic complications; however, diabetic ocular complications in the animal model have not been fully investigated. Previously, we reported that SDT fatty rats develop diabetic cataract, which well mimics the cataract formation in patients with diabetes. (Kikuchi et al., J Diabetes Res., 2020). In the current study, we further investigated the diabetic retinal complications in SDT fatty rats.
Methods :
SDT fatty rats (24 weeks old, male) and age-matched Sprague Dawley (SD) rats were used in this study. Retinal capillaries were isolated by trypsin digestion, and capillary diameter and the retinal capillary pericyte/endothelial cell (P/E) ratio were assessed. Immunostaining for leukocyte adhesion molecules, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), was performed.Real-time PCR and Magnetic Luminex assay were performed to investigate the alteration of the inflammation-related molecules, i.e., monocyte chemotactic protein-1 (MCP-1), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the retina of SDT fatty rats.
Results :
The retinal capillary diameter significantly increased in SDT fatty rats (7.74±0.16 μm, n=5) compared to SD rats (6.42±0.23 μm, n=5, p<0.01). The P/E ratio was significantly lower in the retinal capillaries of SDT fatty rats (0.42±0.04, n=5) than those of SD rats (0.61±0.01, n=5, p<0.01). ICAM-1 and VCAM-1 were immunostained in the retinal vessels of SDT fatty rats. mRNA expression levels of Mcp1, Il1b and Tnf were significantly upregulated in the retina of 24-week-old SDT fatty rats (Mcp1, P<0.01; Il1b, P<0.05; Tnf, P<0.01). The protein levels of MCP-1, IL-1β and TNF-α were also significantly increased in the retina of SDT fatty rats than those of SD rats (MCP-1, P<0.01; IL-1β, P<0.05; TNF-α, P<0.01, n=5 each).
Conclusions :
The present study demonstrated that SDT fatty rats exhibited early diabetic changes in the retina, indicating that SDT fatty rats serve as a potential animal model in researches on the pathogenesis of human diabetic retinopathy.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.