Leukostasis and pigment epithelium-derived factor in rat modelsof diabetic retinopathy

[摘要] Purpose: Spontaneously diabetic Torii (SDT) rats, an animal model oftype 2 diabetes, have a low incidence of neovascular formation and anabsence of non-perfused areas in their retinas at the proliferativestage that presents tractional retinal detachment with fibrousproliferation. The aim of this study was to determine whetherleukostasis is present in the retina, to evaluate the levels of pigmentepithelium-derived factor (PEDF) and intracellular adhesion molecule-1(ICAM-1) levels in the blood of SDT rats, and to examine the effects ofPEDF on leukostasis.Methods: SDT rats, streptozotocin-induced diabetic (STZ) rats, andcontrol Sprague-Dawley (SD) rats were studied. The index of leukostasisin the retina was determined immunohistochemically by counting thenumber of labeled adherent leukocytes. The levels of PEDF and thesoluble intracellular adhesion molecule (sICAM)-1 in the plasma weremeasured. To investigate the effect of PEDF and vascular endothelialgrowth factor (VEGF) on leukostasis, the adhesion of monocytes to humanumbilical vein endothelial cells (HUVECs) was assayed in vitro.Results: SDT and STZ diabetic rats showed a significant increase ofretinal leukostasis compared to that of control SD rats, but SDT ratshad noteworthy lower levels of leukostasis than STZ rats in long termexperiments. The sICAM-1 levels and PEDF expression were up-regulated inboth STZ and SDT rats, but the SDT rats showed significantly higherlevels of PEDF than STZ rats. In vitro studies showed that exposure ofHUVECs to VEGF increased the number of adhering monocytes, and PEDFinhibited the VEGF-induced leukostasis in a dose-dependent manner.Conclusions: The inhibition of the VEGF-induced leukostasis by PEDFis most likely responsible for the low incidence of capillary occlusionand retinal neovascularization in SDT rats.

[学科分类] 生物化学/生物物理