Myopia, also known as nearsightedness, is one of the prime reasons for vision impairment worldwide. Atropine in topical ophthalmic solutions (e.g., 0.01% atropine sulfate eye drops) is the primary medical treatment for controlling myopia, especially for pseudomyopia or true myopia in rapid progress. However, aqueous atropine solution is unstable and easily breaks down to tropic acid, which will result in vision blur. Drug-eluting contact lenses (CLs) have been explored as a potentially superior alternative to effectively control the drug release and improve the drug efficacy. In this work, an atropine-eluting contact lens was developed by encapsulating an atropine implant in a silicon-based contact lens, towards functioning in vision correction and controlling myopia. The safety and effectiveness of this atropine-eluting contact lens were verified with rabbit and guinea pig models. The results showed that the lenses reduced the side effects like mydriasis and no other adverse events were observed in rabbit eyes. More importantly, atropine-loaded lenses could effectively delay the progress of form-deprivation myopia with guinea pig eyes as the model. Thus, we concluded that atropine-eluting CLs prepared by implantation technology may be an option for the treatment of myopia.
Background: Diabetic retinopathy (DR) is one of the most serious microvascular complications of diabetes mellitus. Retinal neovascularization (RNV) under the continuous influence of hyperglycemia is the main cause of blindness in DR patients, but the mechanism of neovascularization has not been fully elucidated yet. In this study, we investigated the effect of exosomes secreted by human retinal pigmented epithelial (ARPE-19) cells at high glucose concentrations on in vitro angiogenesis of human umbilical vein endothelial cells(HUVECs). The role of exosomal miRNAs in the pathogenesis of DR was explored.Methods: Exosomes were extracted from the supernatant of ARPE-19 cells by differential centrifugation. Confocal microscopy was used to observe whether exosomes could be taken up by HUVEC, and the effects of exosomes on HUVEC angiogenesis under three sets of glucose concentrations were observed by co-culture and in vitro angiogenesis. The expression of 21 candidate miRNAsin exosomes and 22 candidate mRNAsin HUVEC after the effect of three sets of glucose concentrations was examined by qRT-PCR. Prediction of miRNA-targeted regulatory mRNAs by bioinformatics. Regulation of miR-135a-5p expression by transfection of small interfering RNA and miRNA mimic. Western blot and qRT-PCR were performed to detect the expression of SITR1.Results: Confocal images show that high glucose-induced exosomes (HG-exo) can be taken up by HUVECs and promote the tube formation of HUVECs in vitro. The results of qRT-PCR showed that the expressions of miR-9-3p, miR-135a-5p, miR-134-5p, miR-195-3p, miR-181c-5p and miR-132-3p were upregulated in HG-exo (P < 0.05). The expressions of HIF-1α, SIRT1 and SPRED1 in HUVECs co-cultured with HG-exo were decreased (P < 0.05). Bioinformatics analysis indicated that miR-135a-5p binds to the SIRT1 3'UTR region. We verified this by transfection experiments and showed that miR-135a-5p could inhibit the expression of SIRT1 mRNA and protein.Conclusions:In the presence of high glucose, exosomal miR135a-5p secreted by ARPE-19 cells targeted the SIRT1 3'UTR region and inhibited SIRT1 expression, which in turn promoted neovascularization.
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