ABSTRACT
AIM: To generate a mouse model for slow progressive retinal neovascularisation through vascular endothelial growth factor (VEGF) upregulation. METHODS: Transgenic mice were generated via microinjection of a DNA construct containing the human VEGF165 (hVEGF) gene driven by a truncated mouse rhodopsin promoter. Mouse eyes were characterised clinically and histologically and ocular hVEGF levels assayed by ELISA. RESULTS: One transgenic line expressing low hVEGF levels showed mild clinical changes such as focal fluorescein leakage, microaneurysms, venous tortuosity, capillary non-perfusion and minor neovascularisation, which remained stable up to 3 months postnatal. Histologically, there were some disturbance and thinning of inner and outer nuclear layers, with occasional focal areas of neovascularisation. By contrast, three other lines expressing high hVEGF levels presented with concomitantly severe phenotypes. In addition to the above, clinical features included extensive neovascularisation, haemorrhage, and retinal detachment; histologically, focal to extensive areas of neovascularisation associated with retinal folds, cell loss in the inner and outer nuclear layers, and partial retinal detachment were common. CONCLUSIONS: The authors generated four hVEGF overexpressing transgenic mouse lines with phenotypes ranging from mild to severe neovascularisation. These models are a valuable research tool to study excess VEGF related molecular and cellular changes and provide additional opportunities to test anti-angiogenic therapies.
Subject(s)
Mice, Transgenic/genetics , Retinal Neovascularization/genetics , Vascular Endothelial Growth Factor A/genetics , Animals , Diabetic Retinopathy/genetics , Diabetic Retinopathy/pathology , Disease Models, Animal , Fluorescein Angiography/methods , Humans , Mice , Mice, Inbred C57BL , Phenotype , Retinal Detachment/genetics , Retinal Detachment/pathology , Retinal Hemorrhage/genetics , Retinal Hemorrhage/pathology , Retinal Neovascularization/pathology , Retinal Vessels/pathology , Retinal Vessels/physiology , Up-Regulation/geneticsSubject(s)
Bone Density/physiology , Bone and Bones/metabolism , Lupus Erythematosus, Systemic/metabolism , Tomography, X-Ray Computed , Adult , Bone and Bones/diagnostic imaging , Disease Progression , Female , Follow-Up Studies , Humans , Lupus Erythematosus, Systemic/diagnostic imaging , Male , Prognosis , Severity of Illness IndexABSTRACT
Vertebral trabecular bone mineral density (BMD) was measured by quantitative computed tomography (QCT) in 1061 subjects (610 females and 451 males aged from 7 to 91 and from 12 to 89, respectively) with known history of diseases or taking medicines affecting bone metabolism. Peak BMD values in our patients were observed at the age of 20-29 years with further gradual decrement in men and more steep in women. Negative relationship between BMD and age was r = -0.991 for men and r = -0.968 for women. Analyzing BMD changes by decades we observed the largest decrement in men after 60 (13.1% for 60-69 and 14.1% for 70-79 years of age) and in women after 50 (22.5% for 50-59, 22.1% for 60-69 and 20.8% for 70-79 years) which was most probably due to decline in sex hormones production that is known to significantly influence bone metabolism. This was confirmed by BMD values three-phase approximation in women showing the lowest rate of calcium loss by trabecular bone in reproductive period (1.9 mg/cm3/yr) and the highest in perimenopause (3.98 mg/cm3/yr). Annual calcium loss in postmenopause was 2.22 mg/cm3.
