To investigate the effect of glucose transporter-1 (GLUT1) inhibition on diabetic retinopathy, we divided forty-eight mice into scrambled siRNA, diabetic scrambled siRNA, and GLUT1 siRNA (intravitreally injected) groups. Twenty-one weeks after diabetes induction, we calculated retinal glucose concentrations, used electroretinography (ERG) and histochemical methods to assess photoreceptor degeneration, and conducted immunoblotting, leukostasis and vascular leakage assays to estimate microangiopathy. The diabetic scrambled siRNA and GLUT1 siRNA exhibited higher glucose concentrations than scrambled siRNA, but GLUT1 siRNA group concentrations were only 50.05% of diabetic scrambled siRNA due to downregulated GLUT1 expression. The diabetic scrambled siRNA and GLUT1 siRNA had lower ERG amplitudes and ONL thicknesses than scrambled siRNA. However, compared with diabetic scrambled siRNA, GLUT1 siRNA group amplitudes and thicknesses were higher. Diabetic scrambled siRNA cones were more loosely arranged and had shorter outer segments than GLUT1 siRNA cones. ICAM-1 and TNF-α expression levels, adherent leukocyte numbers, fluorescence leakage areas and extravasated Evans blue in diabetic scrambled siRNA were higher than those in scrambled siRNA. However, these parameters in the GLUT1 siRNA were lower than diabetic scrambled siRNA. Together, these results demonstrate that GLUT1 siRNA restricted glucose transport by inhibiting GLUT1 expression, which decreased retinal glucose concentrations and ameliorated diabetic retinopathy.Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus (DM). DR often results in decreased vision and even blindness caused by macular edema, retinal detachment, and vitreous hemorrhage. The number of patients with diabetes may grow to 642 million in 2040 1 . DR has been recognized as a microangiopathy, as well as a neurodegenerative disease. Although the detailed mechanism underlying DR is unclear, two major global multicenter studies on diabetes, DCCT 2 and UKPDS 3 , have revealed that a long-term high blood glucose level is the decisive factor for DR development. Moreover, excessive generation of retinal oxidative stress products 4 , activated protein kinase C 5 , and increased synthesis of glycosylated end products 6 under the environment of high blood glucose levels initiate the impairment of retinal tissues and cells 4 . Since lesions are induced by high blood glucose levels, we hypothesize that DR progression can be relieved by restricting glucose transfer into the retina, thereby decreasing its local glucose content. Glucose transporter-1 (GLUT1) is the only currently known carrier of glucose through the blood-retinal barrier and is also responsible for the distribution of glucose in ganglion cells, photoreceptor cells, and Müller cells in the retina; GLUT1 is primarily expressed in the vascular endothelial cells of the inner blood-retinal barrier and retinal pigment epithelial cells of the outer blood-retinal barrier 7 . GLUT1 was identified as a promising target...

The aim of the present study was to investigate the effect of homocysteine (Hcy) in on human trabecular meshwork cells (HTMCs). A total of 41 patients with primary open-angle glaucoma (POAG) and 53 patients with senile cataracts (control group) were recruited. Plasma and aqueous humor samples were collected and the Hcy concentrations were determined using enzymatic cycling assays. In cell experiments, normal HTMCs were passaged and randomly divided into a blank control group, a normal HTMC group and experimental groups, which were treated with different concentrations of Hcy. The HTMC activities were detected using the Cell Counting Kit-8 method and the HTMC mitochondrial membrane potential (MMP) was detected using JC-1 staining. Reactive oxygen species (ROS) released by trabecular meshwork cells was detected using flow cytometry and superoxide dismjutase-1 (SOD1) expression was detected using immunoblotting. The results revealed that the concentration of Hcy in the plasma and aqueous humor of the POAG group (14.44±0.86 and 1.60±0.27 µmol/l, respectively) was significantly higher compared with the control group (10.82±0.29 and 0.69±0.39 µmol/l). All tested concentrations (30, 100, 300 and 1,000 µmol/l) of Hcy reduced the MMP in HTMCs and inhibited HTMC proliferation in a dose-dependent manner. ROS production by HTMCs significantly increased with increased concentrations of Hcy, whereas SOD1 expression significantly decreased in a dose-dependent manner. In summary, patients with POAG were demonstrated to have increased concentrations of Hcy in the plasma and aqueous humor. High concentrations of Hcy in HTMCs induced an oxidative stress state, thereby further inhibiting HTMC proliferation. The results of the present study demonstrate that Hcy may be a potential treatment target in patients with POAG.

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Juglonols A-C (1-3), three new juglone derivatives possessing a hydroxyethyl side chain, were isolated from an organic extract of the immature exocarps of Juglans mandshurica together with five known tetralones (4-8). Their structures were elucidated by extensive spectroscopic analyses and comparison with literature data. The new juglone derivatives exhibited inhibitory activities towards a panel of bacteria and fungi, as well as cancer cell lines. In contrast, the known tetralone homologues (4-8) appeared to be much less efficacy.