Upregulation of histone H3 caused by CRYAA may contribute to the development of age-related cataract

Objective:Age-relate cataract(ARC)is a disease of the eyes with no effective drugs to prevent or treat patients.The aim of the present study is to determine whether histone H3,αA-crystallin(CRYAA),β-galactosidase(GLB1),and p53 are involved in the pathogenesis of ARC.Methods:A total of 99 anterior lens capsules(ALCs)of patients with ARC of various nuclear grades,ultraviolet models of ALCs,and two human lens epithelial cell lines(FHL-124 and SRA01/04)were used,and the expression of histone H3,CRYAA,GLB1,and p53 were detected by immunoblotting and reverse transcription and real time-quantitative polymerase chain reaction.The association between CRYAA with histone H3,GLB1,and p53 was assessed in FHL-124 and SRA01/04 cells following CRYAA overexpression.Results:Histone H3 and p53 in ALCs of patients with ARC were up-regulated in a grade-dependent manner,and the expression of CRYAA showed a positive association with histone H3,p53,and GLB1.In UV models of ALCs and human lens epithelial cell lines,the expression levels of histone H3,cell apoptosis factors(Bax/Bcl-2,cleaved caspase-3),and inflammation factors(interleukin-6,tumor necrosis factor-α)were all up-regulated.Furthermore,transfection of CRYAA in FHL-124 cells induced overexpression of histone H3.Conclusion:CRYAA-mediated upregulation of histone H3 may be involved in the pathogenesis of ARC.p53 may also have a role in ARC development,but not via the CRYAA-histone H3 axis.The results of the present study may assist in improving our understanding of the pathogenesis of ARC and in identifying potential targets for treatment.

Genetic mutations and molecular mechanisms of Fuchs endothelial corneal dystrophy

Background:Fuchs endothelial corneal dystrophy is a hereditary disease and the most frequent cause of corneal transplantation in the worldwide.Its main clinical signs are an accelerated decrease in the number of endothelial cells,thickening of Descemet’s membrane and formation of guttae in the extracellular matrix.The cornea’s ability to maintain stromal dehydration is impaired,causing painful epithelial bullae and loss of vision at the point when the amount of corneal endothelial cells cannot be compensated.At present,apart from corneal transplantation,there is no other effective treatment that prevents blindness.Main text:In this review,we first summarized the mutations of COL8A2,TCF4,TCF8,SLC4A11 and AGBL1 genes in Fuchs endothelial corneal dystrophy.The molecular mechanisms associated with Fuchs endothelial corneal dystrophy,such as endoplasmic reticulum stress and unfolded protein response pathway,oxidative stress,mitochondrial dysregulation pathway,apoptosis pathway,mitophagy,epithelial-mesenchymal transition pathway,RNA toxicity and repeat-associated non-ATG translation,and other pathogenesis,were then explored.Finally,we discussed several potential treatments related to the pathogenesis of Fuchs endothelial corneal dystrophy,which may be the focus of future research.Conclusions:The pathogenesis of Fuchs endothelial corneal dystrophy is very complicated.Currently,corneal transplantation is an important method in the treatment of Fuchs endothelial corneal dystrophy.It is necessary to continuously explore the pathogenesis of Fuchs endothelial corneal dystrophy and establish the scientific foundations for the development of next-generation corneal therapeutics.

Cost-Utility Analysis of Screening for Diabetic Retinopathy in China

Background.Diabetic retinopathy(DR)has been primarily indicated to cause vision impairment and blindness,while no studies have focused on the cost-utility of telemedicine-based and community screening programs for DR in China,especially in rural and urban areas,respectively.Methods.We developed a Markov model to calculate the cost-utility of screening programs for DR in DM patients in rural and urban settings from the societal perspective.The incremental cost-utility ratio(ICUR)was calculated for the assessment.Results.In the rural setting,the community screening program obtained 1 QALY with a cost of$4179(95%CI 3859 to 5343),and the telemedicine screening program had an ICUR of$2323(95%CI 1023 to 3903)compared with no screening,both of which satisfied the criterion of a significantly cost-effective health intervention.Likewise,community screening programs in urban areas generated an ICUR of$3812(95%CI 2906 to 4167)per QALY gained,with telemedicine screening at an ICUR of$2437(95%CI 1242 to 3520)compared with no screening,and both were also cost-effective.By further comparison,compared to community screening programs,telemedicine screening yielded an ICUR of 1212(95%CI 896 to 1590)per incremental QALY gained in rural setting and 1141(95%CI 859 to 1403)in urban setting,which both meet the criterion for a significantly cost-effective health intervention.Conclusions.Both telemedicine and community screening for DR in rural and urban settings were cost-effective in China,and telemedicine screening programs were more cost-effective.