Genetic and environmental factors strongly influence risk,severity and progression of age-related macular degeneration

Age-related macular degeneration(AMD)is characterized by complex interactions between genetic and environmental factors.Here we genotyped the selected 25 single-nucleotide polymorphisms(SNPs)in 983 cases with advanced AMD and 271 cases with intermediate AMD and build an AMD life-risk score model for assessment of progression from intermediate to advanced AMD.We analyzed the performance of the prediction model for geographic atrophy progressors or choroidal neovascularization progressors versus non-progressors based on the 25 SNPs plus body mass index and smoking status.Our results suggest that a class prediction algorithm can be used for the risk assessment of progression from intermediate to late AMD stages.The algorithm could also be potentially applied for therapeutic response,and toward personalized care and precision medicine.

Inhibitory effect of lanosterol on cataractous lens of cynomolgus monkeys using a subconjunctival drug release system Keke

Background:To evaluate the effect of lanosterol on cataractous lens of cynomolgus monkeys using a subconjunctival drug release system.Methods:Nine elder cynomolgus monkeys were used,consisting of three monkeys without cataract as controls,three monkeys with naturally occurring cortical cataract,and three monkeys with nuclear cataract as intervention groups.Nanoparticulated thermogel with lanosterol and fluorescein was administered by subconjunctival injection in the monkeys with cataract.Fluorescence changes of injected thermogel and cataract progression were observed.Lanosterol concentration in aqueous humor,solubility changes in lens proteins,and oxidative stress levels were analyzed in the lenses of the control and intervention groups.Results:Injected thermogel showed decreased fluorescence during follow up.Lanosterol concentration in aqueous humor increased in the first 2 weeks and then gradually decreased,which was in accordance with the changes in cortical lens clarity.However,lenses with nuclear opacification showed little change.In the cortical region of lenses with cortical cataract,solubility ofα-crystallin was significantly increased after administration of lanosterol,as well as the reduction of oxidative stress.Conclusions:We demonstrated the effect of lanosterol on cataract progression based on in vivo models of primates.Lanosterol showed a short-term and reliable reversal effect on reducing cataract severity in cortical cataract in the early stages,possibly due to the increase in the solubility of lens proteins and changes in the oxidative stress status.Lanosterol administration using subconjunctival drug release system could be a promising nonsurgical approach for future clinical studies of cataract prevention and treatment.