No abstract

Diabetic retinopathy (DR) is one of the serious complications that occur in diabetic patients that frequently causes blindness. Long non-coding RNAs (lncRNAs) have been associated with DR pathology. This study aimed to determine the underlying mechanism of lncRNA maternally expressed gene 3 (MEG3) in association with DNA methyltransferase 1 (DNMT1) in the endothelial-mesenchymal transition (endMT) that occurs in DR. A rat model of DR was induced by streptozotocin (STZ) injection, and high glucose (HG)-induced cell model was established by exposing microvascular endothelial cells obtained from retina of rats to HG. Subsequently, MEG3 was overexpressed in rat and cell models to characterize its impact on endMT in DR and the involvement of the PI3K/AKT/mTOR signaling pathway. Furthermore, the methylation level of MEG3 promoter region was determined with the application of methylation-specific polymerase chain reaction, followed by Chromatin immunoprecipitation assay for methyltransferase enrichment. Finally, we examined the regulation of DNMT1 on MEG3 methylation and endMT in the HG-induced cell model. The results obtained revealed downregulated MEG3 expression in DR rat and cell models. Overexpressed MEG3 was shown to suppress endMT in DR rat and cell models through the inhibition of the PI3K/AKT/mTOR signaling pathway. Notably, DNMT1 could promote MEG3 promoter methylation to inhibit MEG3 expression by recruiting methyltransferase, which activated the PI3K/AKT/mTOR signaling pathway to accelerate endMT in DR. These findings further highlighted the inhibitory effect of MEG3 on endMT in DR, thus presenting a novel therapeutic target candidate for DR treatment.

ABSTRACT.To perform a comprehensive evaluation and comparison of tear function in diabetic and non-diabetic patients. Research related to tear function in diabetic and non-diabetic patients was gathered using PubMed, EBSCO, OVID. Two reviewers independently conducted the literature search. The quality assessment and the data extraction were performed in accordance with exclusion criteria and cross-checking. RevMan 5.1.7 software was used for the meta-analysis. The tear film break-up time was studied in eight articles with a total of 1449 samples. Through a random-effects model analysis, the combined weighted mean difference (WMD) was )4.44 [)5.87, )3.01]. The time in diabetic patients was shorter than that in the non-diabetic group (p < 0.00001). The basal tear secretion test was studied in seven articles with a total of 949 samples. The combined WMD was )3.96 [)5.70, )2.23], and the difference between the diabetic group and control group was statistically significant (p < 0.00001). The total tear secretion test was studied in five articles with a total of 921 samples. The combined WMD was )3.96 [)7.43, )0.50]. The difference between the diabetic and control groups was statistically significant (p = 0.03). The corneal sensitivity was compared in eight studies with a total of 976 samples. Through a random-effects model analysis, the standardized mean difference (SMD) was )5.14 [)6.99, )3.29]. The corneal sensitivity was lower in diabetic patients than the control group (p < 0.00001). Our study suggests that the tear functions are worse in diabetic patients compared with the control group. Moreover, patients with PDR are more predisposed to impaired tear functions.

Retinal dystrophy is an inherited, heterogeneous, chronic and progressive disorder of visual functions. The mutations of patients with autosomal recessive retinal retinopathy cone‐and‐rod dysfunction and macular dystrophy have not been well described in the Chinese population. In this study, a three‐generation Chinese retinal dystrophy family was recruited. Ophthalmic examinations were performed. Targeted next generation sequencing (TGS) was used to identify causative genes, and Sanger sequencing was conducted to verify candidate mutations and co‐segregation. Reverse transcription (RT)‐PCR was applied to investigate the spatial and temporal expression patterns of cdhr1 gene in mouse. A novel, homozygous, deleterious and nonsense variant (c.T1641A; p.Y547*) in the CDHR1 gene was identified in the family with autosomal recessive retinal dystrophy, which was co‐segregated with the clinical phenotypes in this family. RT‐PCR analysis revealed that cdhr1 is ubiquitously expressed in eye, particularly very high expression in retina; high expression in lens, sclera, and cornea; and high expression in brain. In conclusion, our study is the first to indicate that the novel homozygous variant c.T1641A (p.Y547*) in the CHDR1 gene might be the disease‐causing mutation for retinal dystrophy in our patient, extending its mutation spectrums. These findings further the understanding of the molecular pathogenesis of this disease and provide new insights for diagnosis as well as new implications for genetic counselling.