ABSTRACT
OBJECTIVE: To investigate the effect of hypoxia inducing factor (HIF)-1α on the expression of vascular endothelial growth factor (VEGF) and angiogenesis in diabetic retinopathy. PATIENTS AND METHODS: 8-week healthy SD rats were used for the experiments. Under systemic anesthesia condition, control rats received a saline injection into the left ocular body (control A group), and 2 µl antisense oligonucleotides (ASODN) (10 µmol/L) into right eye (control B group). Model rats received a saline injection into the left eye (model A group), and 2 µl ASODN (10 µmol/L) into the right eye (model B group). Rats received an intraocular injection of HIF-1α ASODN for 2, 4, and 6 weeks (A1, A2, A3, B1, B2, B3, respectively). Retinal vessel development was observed by ADP staining. Vascular endothelial cells penetrating retinal inner membrane were counted. Immunohistochemistry was used to detect expressions of VEGF and HIF-1α proteins in the retina. RESULTS: Prominent angiogenesis and hyperplasia were found in model A group. Relatively fewer newly formed vessels were shown in model group B. However, no significant change of retinal vascular morphology was presented in control group. Of note, the vascular endothelial cell counts, VEGF and HIF-1α contents were significantly increased in model group (p < 0.05). After treatment with HIF-1α ASODN, lower endothelial cell counts was found in model B group (p < 0.05 comparing to model A). VEGF expression in model B group was significantly decreased, among which, model B3 was observed with lower cell counts than model B1 or B2 (p < 0.05 comparing to model A). Injection of HIF-1α ASODN significantly suppressed HIF-1α level in model B in a time-dependent manner. CONCLUSIONS: Retinal angiogenesis is closely related with increasing level of HIF-1α. Inhibition of HIF-1α suppressed VEGF expression and deterred angiogenesis in a time-dependent manner. This provided novel insights for treating diabetic retinopathy.
Subject(s)
Diabetic Retinopathy/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/administration & dosage , Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis , Neovascularization, Pathologic/metabolism , Vascular Endothelial Growth Factor A/biosynthesis , Animals , Diabetic Retinopathy/genetics , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Gene Expression , Hypoxia-Inducible Factor 1, alpha Subunit/drug effects , Injections, Intraocular , Male , Rats , Rats, Sprague-Dawley , Retina/drug effects , Retina/metabolism , Retinal Vessels/drug effects , Retinal Vessels/metabolism , Vascular Endothelial Growth Factor A/geneticsABSTRACT
Toxoplasmosis, caused by the protozoan parasite Toxoplasma gondii, is one of the most common parasitic infections in humans. Primary infection in pregnant women can be transmitted to the fetus leading to miscarriage or congenital toxoplasmosis. Carefully designed nationwide seroprevalence surveys and case-control studies of risk factors conducted primarily in Europe and America, have shaped our view of the global status of maternal and congenital infection, directing approaches to disease prevention. However, despite encompassing 1 in 5 of the world's population, information is limited on the status of toxoplasmosis in China, partly due to the linguistic inaccessibility of the Chinese literature to the global scientific community. By selection and analysis of studies and data, reported within the last 2 decades in China, this review summarizes and renders accessible a large body of Chinese and other literature and aims to estimate the seroprevalence in Chinese pregnant women. It also reviews the prevalence trends, risk factors, and clinical manifestations. The key findings are (1) the majority of studies show that the overall seroprevalence in Chinese pregnant women is less than 10%, considerably lower than a recently published global analysis; and (2) the few available appropriate studies on maternal acute infection suggested an incidence of 0·3% which is broadly comparable to studies from other countries.
