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M. Matsuoka, N. Ogata, M. Matsumura; Leukostasis and Expression of Pigment Epithelium–Derived Factor in Retinopathy of Diabetic Rats . Invest. Ophthalmol. Vis. Sci. 2005;46(13):414.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Spontaneously diabetic Torii (SDT) rats are a new animal model of type 2 diabetes. We previously reported that SDT rats developed diabetic retinopathy characterized with a low incidence of retinal neovascularization and poor development of non–perfused areas. We also found that high levels of pigment epithelium–derived factor (PEDF) were expressed in the diabetic retina. In this study, we investigated the retinal leukostasis and the levels of intercellular adhesion molecule–1 (ICAM–1) and PEDF in the plasma of SDT rats. Methods: The eyes were obtained from 20– (early onset of diabetes and without retinopathy) , and 60–week–old (long–term affection of diabetes and with retinopathy) male SDT rats and age–matched control SD rats. The retinal vasculature was examined by fluorescein–dextran angiography. Leucocytes and endothelial cells were labeled with FITC–conjugated concanavalin–A lectin and leucocytes adherent to retinal vessels were counted. The levels of ICAM–1 were measured by ELISA and the levels of PEDF were detected by Western blotting analysis. Results: The retinal leukostasis was increased in SDT rats by 6.8–fold compared to that of controls (p<0.05). Alternatively, the retinal leukostasis in 60–week–old SDT rats did not significantly differ from that of 20–week–old SDT rats. The level of ICAM–1 was increased in SDT rats by 2.4–fold compared to that of controls (20.3ng/ml, p<0.05). In addition, the level of ICAM–1 in 60–week–old SDT rats was increased by 1.6–fold (p<0.05) compared with that of 40–week–old SDT rats. That is, the retinal leukostasis was not increased in 60–week–old SDT rats compared to that of 20–week–old SDT rats, although the level of ICAM–1 was significantly increased in 60–week–old SDT rats. The level of PEDF was increased in SDT rats by 1.8–fold compared to that of controls (p<0.05). Conclusions: The low increase of retinal leukostasis in SDT rats may resulte in diabetic retinopathy characterized by poor development of non–perfused areas. It is more likely that high levels of PEDF may prevent the increase of leukostasis, because PEDF prevents advanced glycation end products–induced monocyte chemoattractant protein–1, a chemokine that induces the infiltration of monocytes and macrophages into tissues.
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