Title The expression of the Slit-Robo signal in the retina of diabetic rats and the vitreous or fibrovascular retinal membranes of patients with proliferative diabetic retinopathy
Authors Zhou, Weiyan
Wang, Hongya
Yu, Wenzhen
Xie, Wankun
Zhao, Min
Huang, Lvzhen
Li, Xiaoxin
Affiliation Shandong Univ, Dept Ophthalmol, Shandong Prov Hosp, Jinan, Shandong, Peoples R China.
Peking Univ, Peoples Hosp, Dept Ophthalmol, Beijing Key Lab Diag & Therapy Retinal & Choroid, Beijing, Peoples R China.
Shandong Univ, Dept Clin Lab, Shandong Prov Hosp, Jinan, Shandong, Peoples R China.
Keywords ENDOTHELIAL GROWTH-FACTOR
PIGMENT EPITHELIAL-CELLS
TUMOR ANGIOGENESIS
AXON GUIDANCE
NEOVASCULARIZATION
ROUNDABOUT
MIGRATION
RECEPTOR
PATHOGENESIS
ADHESION
Issue Date 2017
Publisher PLOS ONE
Citation PLOS ONE.2017,12(10).
Abstract Purpose The Slit-Robo signal has an important role in vasculogenesis and angiogenesis. Our study examined the expression of Slit2 and its receptor, Robo1, in a rat model of streptozotocininduced diabetes and in patients with proliferative diabetic retinopathy. Methods Diabetes was induced in male Sprague-Dawley rats via a single, intraperitoneal injection of streptozotocin. The rats were sacrificed 1, 3 or 6 months after the injection. The expression of Slit2 and Robo1 in retinal tissue was measured by real-time reverse transcription polymerase chain reaction (RT-PCR), and protein levels were measured by western blotting and immunohistochemistry. Recombinant N-Slit2 protein was used to study the effects of Slit2 on the expression of VEGF in vivo. The concentration of Slit2 protein in human eyes was measured by enzyme-linked immunosorbent assay in 27 eyes with proliferative diabetic retinopathy and 28 eyes in control group. The expression of Slit2, Robo1 and VEGF in the excised human fibrovascular membranes was examined by fluorescence immunostaining and semi-quantitative RT-PCR. Results The expression of Slit2 and Robo1 in the retina was altered after STZ injection. Recombinant N-Slit2 protein did not increase the retinal VEGF expression. Vitreous concentrations of Slit2 were significantly higher in the study group than in the control group. In the human fibrovascular membranes of the study group, the co-localization of VEGF with the markers for Slit2 and Robo1was observed. The expression of Slit2 mRNA, Robo1 mRNA, and VEGF mRNA was significantly higher in human fibrovascular proliferative diabetic retinopathy membranes than in the control membranes. Conclusions The alteration of Slit2 and Robo1 expression in the retinas of diabetic rats and patients with proliferative diabetic retinopathy suggests a role for the Slit-Robo signal in the various stages diabetic retinopathy. Further studies should address the possible involvement of the Slit-Robo signal in the pathophysiological progress of diabetic retinopathy.
URI http://hdl.handle.net/20.500.11897/470512
ISSN 1932-6203
DOI 10.1371/journal.pone.0185795
Indexed SCI(E)
Appears in Collections: 人民医院

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