No abstract

This study aimed to investigate the refractive state and optical compositions of preterm children with and without mild retinopathy of prematurity (ROP) and explore the influence of prematurity and mild ROP on the development of refractive state and optical compositions.Preterm children who received fundus screening were recruited, and divided into ROP group and non-ROP group. Term children matched in age were also recruited as controls. Several correspondence indicators were measured before and after ciliary muscle paralysis with 1% cyclopentanone.A total of 250 eyes from 126 patients were included for analysis. The incidence of myopia was the highest in ROP group. The incidence of hyperopia was the highest in control group. The incidence of astigmatism was the highest in ROP group. The corneal astigmatism and mean astigmatism in ROP group and non-ROP group were significantly higher than in control group. Corneal refraction in ROP was markedly higher than in non-ROP group and control group; corneal curvature in ROP group increased significantly as compared with non-ROP group and control group (P < .05). The axial eye length in ROP group and non-ROP group reduced significantly as compared with control group (P < .05). Gestational age had negative relationships with corneal astigmatism (P = .019) and astigmatism (P = .001) and positive relationship with axial eye length (P = .005). Birth weight had negative relationships with corneal astigmatism (P = .001), astigmatism (P < .001), corneal refraction (P = .001), and corneal curvature (P = .001) and positive relationships with axial eye length (P = .001) and spherical equivalent refraction (P = .039). The incidence of myopia increased and that of hyperopia reduced in children over age. In children aged 3 to 4 years, the anterior chamber depth, lens thickness, vitreous thickness, and axial eye length significantly increased as compared with those aged 5 years (P < .05); the vitreous thickness and axial eye length in children aged 5 years increased significantly as compared with those aged 6 years (P < .05).This study shows that preterm children with and without mild ROP are more likely to develop myopia and astigmatism, and low birth weight, prematurity, and ROP may simultaneously affect the development of optical compositions, leading to myopia and astigmatism.

BackgroundFamilial exudative vitreoretinopathy (FEVR) is an inheritable blinding disorder with clinical and genetic heterogeneity. Heterozygous variants in the CTNNB1 gene have been reported to cause FEVR. However, the pathogenic basis of CTNNB1-associated FEVR has not been fully explored.MethodsWhole-exome sequencing was performed on the genomic DNA of probands. Dual-luciferase reporter assay, western blotting and co-immunoprecipitation were used to characterise the impacts of variants. Quantitative real-time PCR, EdU (5-ethynyl-2′-deoxyuridine) incorporation assay and immunocytochemistry were performed on the primary human retinal microvascular endothelial cells (HRECs) to investigate the effect of CTNNB1 depletion on the downstream genes involved in Norrin/β-catenin signalling, cell proliferation and junctional integrity, respectively. Transendothelial electrical resistance assay was applied to measure endothelial permeability. Heterozygous endothelial-specific Ctnnb1-knockout mouse mice were generated to verify FEVR-like phenotypes in the retina.ResultsWe identified two novel heterozygous variants (p.Leu103Ter and p.Val199LeufsTer11) and one previously reported heterozygous variant (p.His369ThrfsTer2) in the CTNNB1 gene. These variants caused truncation and degradation of β-catenin that reduced Norrin/β-catenin signalling activity. Additionally, knockdown (KD) of CTNNB1 in HRECs led to diminished mRNA levels of Norrin/β-catenin targeted genes, reduced cell proliferation and compromised junctional integrity. The Cre-mediated heterozygous deletion of Ctnnb1 in mouse endothelial cells (ECs) resulted in FEVR-like phenotypes. Moreover, LiCl treatment partially rescued the defects in CTNNB1-KD HRECs and EC-specific Ctnnb1 heterozygous knockout mice.ConclusionOur findings reinforced the current pathogenesis of Norrin/β-catenin for FEVR and expanded the causative variant spectrum of CTNNB1 for the prenatal diagnosis and genetic counselling of FEVR.