Pathophysiological characteristics of diabetic ocular complications in spontaneously diabetic torii rat - PubMed (original) (raw)

Pathophysiological characteristics of diabetic ocular complications in spontaneously diabetic torii rat

Tomohiko Sasase. J Ophthalmol. 2010.

Abstract

The Spontaneously Diabetic Torii (SDT) rat, a nonobese type 2 diabetes model, develops severe diabetic retinopathy as result of chronic severe hyperglycemia. Although existing diabetes animal models also develop ocular complications, severe retinal lesions frequently observed in human diabetes patients such as preretinal neovascularization or retinal detachment are not found. Distinctive features in SDT rat are hypermature cataract, tractional retinal detachment with fibrous proliferation, and massive hemorrhaging in the anterior chamber. These pathophysiological changes are caused by sustained hyperglycemic condition and subsequent increased expression of vascular endothelial growth factor (VEGF) in retina, iris, and ciliary body. Although some differences in diabetic retinopathy exist between SDT rats and humans (e.g., a low incidence of neovascular formation and poor development of nonperfused area are found in this animal), SDT rat will be a useful model in studies of the pathogenesis and treatment of diabetic retinopathy.

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Figures

Figure 1

Figure 1

Nonfasting plasma insulin and glucose levels in Spontaneously Diabetic Torii (SDT) rats and control Sprague-Dawley (SD) rats. Diminish of pancreatic _β_-cells evokes hypoinsulinemia (a) and subsequent severe hyperglycemia (b) in SDT rats. Plasma glucose levels sharply increase at 15–20 weeks of age and eventually reach a plateau, approximately 800 mg/dL. Each value represents mean ± S.E.M. (N = 6–8).

Figure 2

Figure 2

Typical ocular observations in control male SD rats (a, c, e, and g) and SDT rats (b, d, f, and h). (a) and (b) macroscopic photographs of eyes. Hypermature cataract is observed 100% in male SDT rats by 40 weeks of age. (c) and (d) histopathological changes in lens and retina at 80 weeks old. Proliferative fibrovascular membrane in vitreous is found around the optic disk. Retina is locally thickened and formed a fold. Disintegration of lens is also observed. H&E stain. (e) and (f) fluorescein angiomicroscopy at 80 weeks of age. Abnormal vascular formation, including venous dilation and meandering vascular networks, is characteristically observed in SDT rats. Extensive fluorescein leakage is found around the optic disk. (g) and (h) anti-VEGF staining of iris at 80 weeks of age. VEGF immunoreactivity is increased in iris of SDT rats. This may cause a massive hemorrhage on iris in some severe cases.

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