Axitinib inhibits retinal and choroidal neovascularization in in vitro and in vivo models

AbstractAge-related Macular Degeneration (AMD) is the leading cause of visual impairment and blindness in the elderly in developed countries. Neovascular/exudative (wet) AMD is the aggressive form of AMD and can involve choroidal neovascularization and vascular leakage. Anti-vascular endothelial growth factor (anti-VEGF) medications have significantly improved treatment of wet-AMD. However, only approximately 40% of patients obtain full benefit from anti-VEGF therapy and the medications are given by intravitreal injection. Axitinib, a small molecule multi-receptor tyrosine kinase inhibitor used for the treatment of advanced renal cell carcinoma, is taken orally and inhibits VEGF activity by blocking VEGF receptors. Axitinib also has the advantage of blocking platelet derived growth factor (PDGF) receptors which play a role in neovascularization. Using in vitro human retinal microvascular endothelial cells (HRMVECs), human brain vascular pericytes (HBVRs), 3D co-culture vessel sprout assay, and in vivo laser induced rat choroidal neovascularization (CNV) models, the effect of axitinib on neovascularization was evaluated. Axitinib inhibited neovascularization better than anti-VEGF and/or anti-hPDGF-B mAb in the in vitro models demonstrating that combined inhibition of both VEGF and PDGF pathways may be synergistic in treating wet-AMD. Additionally, axitinib showed good efficacy at a low dose (0.875 mg/day) in laser-induced CNV model in rats. In conclusion our data shows that axitinib, an inhibitor of VEGF and PDGF-B pathways may be useful in ameliorating wet-AMD therapy

European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that persists into adulthood in the majority of cases. The evidence on persistence poses several difficulties for adult psychiatry considering the lack of expertise for diagnostic assessment, limited treatment options and patient facilities across Europe. METHODS: The European Network Adult ADHD, founded in 2003, aims to increase awareness of this disorder and improve knowledge and patient care for adults with ADHD across Europe. This Consensus Statement is one of the actions taken by the European Network Adult ADHD in order to support the clinician with research evidence and clinical experience from 18 European countries in which ADHD in adults is recognised and treated. RESULTS: Besides information on the genetics and neurobiology of ADHD, three major questions are addressed in this statement: (1) What is the clinical picture of ADHD in adults? (2) How can ADHD in adults be properly diagnosed? (3) How should ADHD in adults be effectively treated? CONCLUSIONS: ADHD often presents as an impairing lifelong condition in adults, yet it is currently underdiagnosed and treated in many European countries, leading to ineffective treatment and higher costs of illness. Expertise in diagnostic assessment and treatment of ADHD in adults must increase in psychiatry. Instruments for screening and diagnosis of ADHD in adults are available and appropriate treatments exist, although more research is needed in this age group

Viscoelastic properties of fresh human lenses under 40 years of age: implications for the aetiology of presbyopia

[[abstract]]AIM: To determine the viscoelastic properties of fresh human lenses obtained from cadavers under 40 years of age. METHODS: 52 intact clear, human lenses were obtained from 26 donors (mean age of 27.5 ± 9.2 years) within 9 ± 4 h of death. The viscoelastic properties of the lens nuclei and 16 of the lens cortices were quantified within 42 ± 10 h of death using a controlled-strain, linear, simple-shear rheometer. RESULTS: The means (± SD) of the viscoelastic properties of the lens nuclei at a frequency of 75 Hz were: elastic shear modulus, G'=11.00 ± 4.67 Pa, viscous shear modulus, G''=24.91 ± 10.98 Pa, magnitude of the complex shear modulus, |G*|=27.23 Pa, dynamic viscosity, η'=0.33 Pa.s, damping ratio, ζ=2.26 and phase shift, δ=66.17°. There was no statistical difference in these measures between the lens cortices and their respective lens nuclei. There was a small age-related statistically significant increase in G', p=0.003, but not G'' or |G*|. CONCLUSIONS: The observed age-related increase in tissue stiffness of the lens nucleus, ~0.4 Pa/year, is too small to account for the 10 dioptre decline in accommodative amplitude in this age group

Viscoelastic shear properties of the fresh porcine lens

[[abstract]]Aim: To determine the viscoelastic properties of the porcine lens Methods: Linear viscoelastic shear properties of the stroma of four porcine lenses were measured within 5 hours post-mortem, using sinusoidal oscillatory shear deformation. The elastic shear modulus, viscous shear modulus, dynamic viscosity, damping ratio, and phase shift of the lenses were quantified by a controlled-strain, linear simple-shear rheometer at frequencies of 10–50 Hz. Results: The mean viscoelastic properties and their standard deviations across the frequencies examined were: the elastic shear modulus, G′ = 6.2±4.0 Pa, the viscous shear modulus, G″ = 19.2±2.5 Pa, the dynamic viscosity, η′ = 0.16±0.1 Pa•sec, the damping ratio ζ = 4.06±1.25, and the phase shift, δ =  76°± 5.6°. Conclusions: The measured viscoelastic shear properties of the porcine lens reflect a low dynamic viscosity with a high damping ratio. The porcine lens is viscoelastic and is more viscous than elastic. The magnitude of the complex shear modulus of the porcine lens, |G*|, is similar to the shear modulus of the young human lens. Understanding these viscoelastic properties of the natural lens may provide guidance in developing a lens substitute capable of accommodation in the post cataract patient