Let-7a-5p represses proliferation, migration, invasion and epithelial-mesenchymal transition by targeting Smad2 in TGF-β2-induced human lens epithelial cells

Transforming growth factor b2 (TGF-b2)/Smad signaling is widely accepted as a key inducer of proliferationand epithelial-mesenchymal transition (EMT) of human lens epithelial cells (LECs), contributing to thedevelopment of posterior capsule opacification (PCO). Increasing evidence shows that microRNAs (miRNAs)play important roles in PCO pathogenesis. Herein, we aimed to explore the role and molecular mechanism oflet-7a-5p on TGF-b2-induced proliferation and EMT in LECs. qRT-PCR was performed to detect theexpression of let-7a-5p and Smad2 mRNA. Western blot was used to determine the Smad2 level and theinduction of EMT. The targeted correlation between let-7a-5p and Smad2 was confirmed using dual-luciferasereporter and RNA immunoprecipitation assays. CCK-8 assay was employed to determine cell proliferation, andtranswell assays were performed to assess cell migration and invasion. We found that TGF-b2 induced EMT ofLECs, and TGF-b2 upregulated Smad2 expression and reduced let-7a-5p expression in LECs. Smad2 was adirect target of let-7a-5p. Moreover, let-7a-5p upregulation repressed proliferation, migration, invasion andEMT in TGF-b2-induced LECs. But, Smad2 expression restoration abrogated the inhibitory effect of let-7a-5pupregulation. In conclusion, our data indicated that let-7a-5p upregulation repressed TGF-b2-induced proliferation, migration, invasion and EMT at least partly by targeting Smad2 in LECs, highlighting that let-7a-5pmight act as a promising therapeutic target to intervene to the progression of PCO.

Experimental study on cyclosporine A drug delivery system in prevention of posterior capsule opacification after intraocular lens implantation in rabbits / 药物分析学报

Objective To study the effect of cyclosporine A drug delivery system (CsA-DDS) on the prevention of posterior capsule opacification (PCO) after experimental intraocular lens implantation in rabbit eyes. Methods Twenty healthy New Zealand white rabbits, whose left eyes and right eyes were used respectively as experiment eyes and controls, were subjected to extracapsular lens extraction and artificial lens implantation. During the operation, CsA-DDS with poly (lactideco-glycolide) as carriers or empty DDS was implanted in the capsular bag for the experimental eyes and controls respectively. After the operation, anterior chamber reaction, intraocular pressure (IOP) and CsA concentration were monitored and twelve weeks after the operation, the eyes were extracted for histopathological and morphological examinations. Results There were no differences between the two groups in conjunctival congestion,IOP change and anterior chamber reaction. PCO was less severe in the experimental eyes than in the controls. Light microscopy revealed that posterior capsular membrane in the experimental eyes was slick, with no obvious proliferation,whereas in the controls, there were lens epithelial cell proliferation and cortex regeneration of different degrees.Morphological examination with electron microscope showed that in the experimental eyes, lens epithelial cells did not function actively and apoptosis occurred, whereas in the controls, epithelial cells presented active function. No marked ultrastructural changes were found in either group. Conclusion Cs-DDS can inhibit PCO after intraocular lens implantation in rabbit eyes and does not have toxic effects on the surrounding ocular tissues. Therefore, it has a good potential for clinical use in prevention of PCO.

Experimental study on cyclosporine A drug delivery system in prevention of posterior capsule opacification after intraocular lens implantation in rabbits / 西安交通大学学报·英文版

Objective: To study the effect of cyclosporine A drug delivery system (CsA-DDS) on the prevention of posterior capsule opacification (PCO) after experimental intraocular lens implantation in rabbit eyes. Methods: Twenty healthy New Zealand white rabbits, whose left eyes and right eyes were used respectively as experiment eyes and controls, were subjected to extracapsular lens extraction and artificial lens implantation. During the operation, CsA-DDS with poly (lactideco-glycolide) as carriers or empty DDS was implanted in the capsular bag for the experimental eyes and controls respectively. After the operation, anterior chamber reaction, intraocular pressure (IOP) and CsA concentration were monitored and twelve weeks after the operation, the eyes were extracted for histopathological and morphological examinations. Results: There were no differences between the two groups in conjunctival congestion, IOP change and anterior chamber reaction. PCO was less severe in the experimental eyes than in the controls. Light microscopy revealed that posterior capsular membrane in the experimental eyes was slick, with no obvious proliferation, whereas in the controls, there were lens epithelial cell proliferation and cortex regeneration of different degrees. Morphological examination with electron microscope showed that in the experimental eyes, lens epithelial cells did not function actively and apoptosis occurred, whereas in the controls, epithelial cells presented active function. No marked ultrastructural changes were found in either group. Conclusion: Cs-DDS can inhibit PCO after intraocular lens implantation in rabbit eyes and does not have toxic effects on the surrounding ocular tissues. Therefore, it has a good potential for clinical use in prevention of PCO.

Posterior Capsule Opacification and Intraocular Lens Design with In-the-bag fixated Posterior Chamber Lens

This study was performed to evaluate the correlationship between posterior capsular opacification and optic configuration of intraocular lens in extracapsular lens extraction with In-the-bag implantation of posterior chamber lens. We retrospectively studied the 455 cases of cataract operations that were performed between January 1993 and January 1995. All were in-the-bag placement and their optic designs were divided into two groups: a group of biconvex lens and a group of convex-plano lens with continuous laser ridge. The incidence of PCO in bicovex lens group was 7.0% and that of convex plano lens with laser ridge group was 7.1%. The difference in the rate of posterior capsular opacification between two groups was not statistically significant. The incidence of Nd: YAG laser posterior capsulotomy revealed 0.0% in continuous ridged group and 2.6% in biconvex group(p>0.05).

Posterior Capsule Opacification and Intraocular Lens Design in Sulcus Fixated Posterior Chamber Lens

Posterior capsule opacification(PCO) is a common complication of cataract surgery. The presence of a posterior chamber intraocular lens has been shown to decrease the incidence of the development of PCO. Moreover, there are evidences that the design of intraocular lens may also alter its development. Extracapsular lens extraction with implantation of posterior chamber lens were operated on a consecutive series of 230 eyes. These were evaluated in the viewpoint of PCO development after surgery. All were sulcus fixed and their optic designs were devided into two groups; a group of convex-plano lens with continuous laser ridge including convex-concave lens and a group of biconvex lens. The incidence of PCO was lower in convex-plano lens with continuous laser ridge group(6.7%) than that of boconvex lens group(18.9%). The incidence of Nd:YAG posterior capsulotomy marked 0.0% in continuous ridged group and 1.8% in biconvex group(p<0.05, p