Residual Lens Epithelial Cells Research Articles

Cascade catalytic multilayer modified intraocular lens for enhanced and safer posterior capsule opacification prevention

Posterior capsule opacification (PCO) is the most common complication after cataract surgery. It is primarily caused by the proliferation, migration, and adhesion of residual lens epithelial cells within the capsular bag following phacoemulsification and intraocular lens (IOL) implantation. Although investigations of surface modification onto IOL have partially reduced PCO development in recent years, there are still challenges in long-term efficacy and intraocular biocompatibility. In this study, a cascade catalytic system is constructed using natural enzymes onto mesoporous silica nanoparticles (MSNs), which are subsequently fixed to the surface of IOL through layer-by-layer self-assemble of alternating positive and negative charges. The cascade catalytic reaction is trigged simply by glucose within the pouch to produce reactive oxygen species (ROS) without introducing any toxic drugs or external energy, attempting to minimize the possible toxic side effects to surrounding tissues. In vivo and in vitro experiments indicate the effective inhibition of PCO and favorable intraocular compatibility of the cascade catalytic platform modified IOL. More importantly, the modified IOL retains good optical performance and imaging quality, demonstrating promising prospects for application. This study provides a new possibility for enhanced and safer PCO prevention, playing great significance in clinical treatment. Statement of SignificanceCascade catalytic nanoparticles-loaded multilayer modified IOL is obtained via LbL technique.The multilayer coating improves both the loading capacity and the activity of the cascade catalytic nanoparticles.The cascade catalytic reaction is trigged by glucose, producing ROS that efficiently induces apoptosis and death of remaining cells on IOL without introducing any toxic drugs or external energy.The innovative IOL provides a promising approach for enhanced and safer prevention of PCO.

Promising Pharmacological Interventions for Posterior Capsule Opacification: A Review.

Phacoemulsification combined with intraocular lens implantation is the primary treatment for cataract. Although this treatment strategy benefits patients with cataracts, posterior capsule opacification (PCO) remains a common complication that impairs vision and affects treatment outcomes. The pathogenesis of PCO is associated with the proliferation, migration, and fibrogenesis activity of residual lens epithelial cells, with epithelial-mesenchymal transition (EMT) serving as a key mechanism underlying the condition. Transforming growth factor-beta 2 (TGF-β2) is a major promotor of EMT, thereby driving PCO development. Most studies have shown that drugs and miRNAs mitigate EMT by inhibiting, clearing, or eliminating LECs. In addition, targeting EMT-related signaling pathways in TGF-β2-stimulated LECs has garnered attention as a research focus. This review highlights potential treatments for PCO and details the mechanisms by which drugs and miRNAs counter EMT.

Long-Term Outcomes of Cataract Surgery: Analysis of Visual Acuity and Intraocular Pressure in a Tertiary Care Center

Abstract: Posterior capsule opacity (PCO) is a common complication following cataract surgery, caused by the proliferation of residual lens epithelial cells. This study aimed to evaluate the long-term effects of Nd:YAG laser capsulotomy on intraocular pressure (IOP) and visual acuity in PCO patients. This was a retrospective descriptive study. Samples were 24 patients diagnosed with PCO who underwent Nd:YAG laser capsulotomy at Prof. Dr. R. D. Kandou Hospital, Manado, from January 1, 2022, to January 1, 2024. The study recorded pre- and post-procedure IOP and best-corrected visual acuity (BCVA) data. Descriptive analysis, including paired t-tests, was used to assess changes in IOP and BCVA over an average follow-up period of 19.2 months. The results showed a statistically significant improvement in BCVA (p=0.000), with mean values improving from 0.72 to 0.27 LogMAR. A significant reduction in IOP was also observed (p=0.015), with long-term IOP remaining stable. A weak correlation was found between follow-up duration and IOP variation (p=0.02). In conclusion, Nd:YAG laser capsulotomy significantly improves visual acuity and stabilizes intraocular pressure in the long term for PCO patients, suggesting its effectiveness in managing post-cataract surgery complications. Keywords: posterior capsule opacity; Nd:YAG laser capsulotomy; intraocular pressure; visual acuity; cataract surgery Methods: A retrospective descriptive study was conducted on 24 patients diagnosed with PCO who underwent Nd capsulotomy at RSUP Prof Dr. R. D. Kandou Central Hospital, Manado, from January 1, 2022, to January 1, 2024. The study recorded pre- and post-procedure IOP and Best-Corrected Visual Acuity (BCVA) data. Descriptive analysis, including paired t-tests, was used to assess changes in IOP and BCVA over an average follow-up period of 19.2 months. Results: The study revealed a statistically significant improvement in BCVA (p = 0.000), with mean values improving from 0.72 to 0.27 LogMAR. A significant reduction in IOP was also observed (p = 0.015), with long-term IOP remaining stable. A weak correlation was found between follow-up duration and IOP variation (p = 0.02). Conclusion: Nd capsulotomy significantly improves visual acuity and stabilizes IOP in the long term for PCO patients, suggesting its effectiveness in managing post-cataract surgery complications.

Oxidative Stress, Glutaredoxins, and Their Therapeutic Potential in Posterior Capsular Opacification.

Posterior capsular opacification (PCO) is the most common long-term complication of cataract surgery. Traditionally, the pathogenesis of PCO involves the residual lens epithelial cells (LECs), which undergo transdifferentiation into a myofibroblast phenotype, hyperproliferation, matrix contraction, and matrix deposition. This process is driven by the marked upregulation of inflammatory and growth factors post-surgery. Recently, research on the role of redox environments has gained considerable attention. LECs, which are in direct contact with the aqueous humour after cataract surgery, are subjected to oxidative stress due to decreased levels of reduced glutathione and increased oxygen content compared to contact with the outer fibre layer of the lens before surgery. In this review, we examine the critical role of oxidative stress in PCO formation. We also focus on glutaredoxins (Grxs), which are antioxidative enzymes produced via deglutathionylation, their protective role against PCO formation, and their therapeutic potential. Furthermore, we discuss the latest advancements in PCO therapy, particularly the development of advanced antioxidative pharmacological agents, and emphasise the importance and approaches of anti-inflammatory and antioxidant treatments in PCO management. In conclusion, this review highlights the significant roles of oxidative stress in PCO, the protective effects of Grxs against PCO formation, and the potential of anti-inflammatory and antioxidant therapies in treating PCO.

Lens capsule advanced glycation end products induce senescence in epithelial cells: Implications for secondary cataracts.

Posterior capsule opacification (PCO) is a common complication after cataract surgery. Residual lens epithelial cells (LECs) on the anterior lens capsule, after cataract surgery, migrate to the posterior lens capsule and undergo transdifferentiation into myofibroblast-like cells. Those cells synthesize excessive amounts of extracellular matrix and contribute to fibrosis during PCO. Cellular senescence, a phenomenon that increases with aging, has been implicated in several fibrotic diseases. Here, we have investigated the prevalence of senescent LECs within the lens posterior capsule and the ability of advanced glycation end products (AGEs) in lens capsules to induce senescence, contributing to PCO. Aged lens capsules from pseudophakic human cadaver eyes showed the presence of senescent LECs. In human capsular bags, LECs showed an age-dependent increase in senescence after 28 days of culture. Human LECs cultured on aged lens capsules for 3 days underwent senescence; this effect was not seen in LECs cultured on young lens capsules. Human LECs cultured on an AGE-modified extracellular matrix (ECM-AGEs) showed an AGE-concentration-dependent increase in the expression of senescence markers and reactive oxygen species (ROS) levels. Treatment with a RAGE antagonist and ROS inhibitor reduced the expression of senescence and fibrotic markers. Additionally, conditioned media from ECM-AGEs-treated cells induced the expression of fibrotic markers in naïve LECs. Together, these suggest that AGEs in the capsule induce senescence of LECs, which triggers the mesenchymal transition of neighboring non-senescent LECs and contributes to PCO.

Human Primary Lens Epithelial Cultures on Basal Laminas Studied by Synchrotron-Based FTIR Microspectroscopy for Understanding Posterior Capsular Opacification.

Human primary lens epithelial cultures serve as an in vitro model for posterior capsular opacification (PCO) formation. PCO occurs when residual lens epithelial cells (LECs) migrate and proliferate after cataract surgery, differentiating into fibroblastic and lens fiber-like cells. This study aims to show and compare the bio-macromolecular profiles of primary LEC cultures and postoperative lens epithelia LECs on basal laminas (bls), while also analyzing bls and cultured LECs separately. Using synchrotron radiation-based Fourier transform infrared (SR-FTIR) (Bruker, Karlsruhe, Germany) microspectroscopy at the Spanish synchrotron light source ALBA, we observed that the SR-FTIR measurements were predominantly influenced by the strong collagen absorbance of the bls. Cultured LECs on bls showed a higher collagen contribution, indicated by higher vas CH3, CH2 and CH3 wagging and deformation, and the C-N stretching of collagen. In contrast, postoperative LECs on bls showed a higher cell contribution, indicated by the vsym CH2 peak and the ratio between vas CH2 and vas CH3 peaks. The primary difference revealed using SR-FTIR is the greater LEC contribution in spectra recorded from postoperative lens epithelia compared to cultured LECs on bls. IR spectra for bl, cultured LECs and postoperative lens epithelia could be valuable for future research.

Unusual after cataracts: A case series

Posterior capsular opacification (PCO) or “after cataract,” a common complication after cataract surgery, occurs due to abnormal proliferation and differentiation of the residual lens epithelial cells in the capsular bag. It can significantly affect visual acuity and contrast sensitivity. Though it cannot be eliminated, meticulous surgery coupled with appropriate intraocular lens selection can definitely reduce the incidence of PCO, especially in young patients undergoing cataract surgery. A routine neodymium-doped yttrium aluminum garnet (Nd:YAG) capsulotomy can solve the problem easily in most of the patients, but some can have atypical presentations due to angle closure from Soemmering’s ring. The purpose of this report is to present unusual after cataracts and the utility of imaging techniques in the diagnosis of the same.

Lens epithelial cell response to polymer stiffness and polymer chemistry.

Posterior capsule opacification (PCO) is the most common complication of cataract surgery, and intraocular lens (IOL) implantation is the standard of care for cataract patients. Induction of post-operative epithelial-mesenchymal transition (EMT) in residual lens epithelial cells (LEC) is the main mechanism by which PCO forms. Previous studies have shown that IOLs made with different materials have varying incidence of PCO. The aim of this paper was to study the interactions between human (h)LEC and polymer substrates. Polymers and copolymers of 2-hydroxyethyl methacrylate (HEMA) and 3-methacryloxypropyl tris (trimethylsiloxy) silane (TRIS) were synthesized and evaluated due to the clinical use of these materials as ocular biomaterials and implants. The chemical properties of the polymer surfaces were evaluated by contact angle, and polymer stiffness and roughness were measured using atomic force microscopy. In vitro studies showed the effect of polymer mechanical properties on the behavior of hLECs. Stiffer polymers increased α-smooth muscle actin expression and induced cell elongation. Hydrophobic and rough polymer surfaces increased cell attachment. These results demonstrate that attachment of hLECs on different surfaces is affected by surface properties in vitro, and evaluating these properties may be useful for investigating prevention of PCO.

Self-assembled coating with a metal-polyphenolic network for intraocular lens modification to prevent posterior capsule opacification

Posterior capsule opacification (PCO) is a main complication after cataract surgery and intraocular lens (IOLs) implantation and is attributed to residual lens epithelial cells (LECs) migrating to the IOL surface and posterior capsules. IOL surface modification has been a newly-developing research filed in recent years; however, the applicability and economical acquisition of modified materials remain unsolved. In this study, we first applied a metal-polyphenolic network coating with a self-assembly technique on the IOL surface by using tannic acid (TA) combined with AlCl3, which are easily acquire and applying on the IOL surface to solve the IOL transmittance affair. Using wound healing and Transwell assay to verify AZD0364 inhibits cell migration ( P < 0.05), the lipopolysaccharide-induced macrophage inflammation model to verify pterostilbene (PTE) inhibits the inflammatory reaction ( P < 0.01). By optimizes its self-assembly coating parameters and calculating its drug release kinetics, we successfully loaded these two drugs on the coating, named TA (AZD0364/PTE) IOL. Its surface morphology characteristics were analyzed by scanning electron microscope, x-ray photoelectron spectrometer and water contact angle. The optical performance was carefully investigated by optical instruments and equipment (n= 3). The in vitro results showed that TA (AZD0364/PTE) IOL can significantly inhibit cell adhesion and acute inflammation (n= 3, P < 0.0001). Importantly, after in vivo implantation for 28 d with eight rabbits PCO models in two groups, the TA (AZD0364/PTE) IOL group maintained clear refracting media and decreased the inflammatory reaction compared with the original IOL group ( P < 0.05). This study provides a new applicable and economical strategy for preventing PCO and offers a reference for the next generation of IOLs that benefit cataract patients.

Identification of Small Molecules for Prevention of Lens Epithelium-Derived Cataract Using Zebrafish.

Cataract is the leading cause of blindness worldwide. It can be treated by surgery, whereby the damaged crystalline lens is replaced by a synthetic lens. Although cataract surgery is highly effective, a relatively common complication named posterior capsular opacification (PCO) leads to secondary loss of vision. PCO is caused by abnormal proliferation and migration of residual lens epithelial cells (LECs) that were not removed during the surgery, which results in interruption to the passage of light. Despite technical improvements to the surgery, this complication has not been eradicated. Efforts are being made to identify drugs that can be applied post-surgery, to inhibit PCO development. Towards the goal of identifying such drugs, we used zebrafish embryos homozygous for a mutation in plod3 that develop a lens phenotype with characteristics of PCO. Using both biased and unbiased approaches, we identified small molecules that can block the lens phenotype of the mutants. Our findings confirm the relevance of zebrafish plod3 mutants' lens phenotype as a model for lens epithelium-derived cataract and add to our understanding of the molecular mechanisms that contribute to the development of this pathology. This understanding should help in the development of strategies for PCO prevention.

Mild Photothermal Therapy Prevents Posterior Capsule Opacification through Cytoskeletal Remodeling.

Cataract is the first leading cause of blindness in the world and posterior capsule opacification (PCO) is the most common long-term complication after surgery. The primary pathogenic processes contributing to PCO are the proliferation and migration of residual lens epithelial cells (LECs). This study aimed to explore the mild photothermal effect on LECs. Interestingly, this work finds that the mild photothermal effect significantly inhibited the proliferation and migration of LECs. The live cell fluorescence imaging reveals that the remodeling of the actin cytoskeleton and cell morphology attributed to the inhibition effect. Further mechanistic studies at molecular level suggest that the mild photothermal effect can regulate the phosphorylation of ERM, YAP, and Cofilin and thereby affect the proliferation and migration of LECs. In order to explore the potential clinical application of mild photothermal therapy for PCO prevention, PDA/PVA gel rings with photothermal effect is prepared by the repeated freeze-thaw method and conducted experiments in vivo, which achieved favorable PCO prevention effect. Overall, this study shows that the mild photothermal effect can regulate the proliferation and migration of LECs through cytoskeletal remodeling and the results of experiments in vivo demonstrate that mild photothermal effect is a promising approach for PCO prevention.

Cascade reaction triggering and photothermal AuNPs@MIL MOFs doped intraocular lens for enhanced posterior capsular opacification prevention

Posterior capsular opacification (PCO) is the most common complication after cataract surgery. Present strategies can’t meet the clinical needs of long-term prevention. This research reports a novel intraocular lens (IOL) bulk material with high biocompatibility and synergistic therapy. Gold nanoparticles (AuNPs) doped MIL-101-NH2 metal–organic frameworks (MOFs) (AuNPs@MIL) was firstly fabricated via in situ reductions. Then the functionalized MOFs were uniformly mixed with glycidyl methacrylate (GMA) and 2-(2-ethoxyethoxy) ethyl acrylate (EA) to form the nanoparticle doped polymer (AuNPs@MIL-PGE), and which was used to fabricate IOL bulk materials. The materials’ optical and mechanical properties with different mass contents of nanoparticles are investigated. Such bulk functionalized IOL material could efficiently remove residual human lens epithelial cells (HLECs) in the capsular bag in the short term, and can prevent PCO on demand in the long run by near-infrared illumination (NIR) action. In vivo and in vitro experiments demonstrate the biosafety of the material. The AuNPs@MIL-PGE exhibits excellent photothermal effects, which could inhibit cell proliferation under NIR and doesn’t cause pathological effects on the surrounding tissues. Such functionalized IOL can not only avoid the side effects of the antiproliferative drugs but also realize the enhanced PCO prevention in clinical practice.

Plasmin-Induced Lens Epithelial Cells Detachment for the Reduction of Posterior Capsular Opacification.

We sought to evaluate the efficacy and safety of plasmin injection in the capsular bag during the cataract operation for the prevention of posterior capsule opacification. Thirty-seven anterior capsular flaps taken from phacoemulsification surgery were immersed in either 1 µg/mL plasmin (plasmin group, n = 27) or phosphate-buffered saline (control group, n = 10) for 2 minutes and photographed after fixation and nuclear staining to compare the numbers of residual lens epithelial cells. In the animal experiments, the plasmin solution was injected into the capsular bag and remained for 5 minutes during hydrodissection or after lens extraction. The degree of posterior capsular opacity of the rabbits at 2 months were photographed by slit lamp biomicroscopy. In HLE-B3 cell culture, the cell detachment rate, proliferation, and apoptosis after the plasmin digestion were analyzed. The residual lens epithelial cell numbers on the capsule after plasmin treatment were 168 ± 190.7/mm2 in the 1 µg/mL plasmin group, which was significantly lower than that of the control (1012 ± 798.8/mm2; P < 0.0001). In a rabbit model, the treatment of plasmin resulted in a significantly clearer posterior capsule compared with that of the control group at 2 months postoperatively. This study suggested that plasmin injection can induce effective lens epithelial cell detachment, which could be a promising adjunctive treatment to further improve the success rate in posterior capsule opacification prevention. Plasmin injection for lens epithelial cell detachment could significantly decrease the number of residual lens epithelial cells. This approach could be a promising treatment incorporating the current treatment approach to further improve the success rate in posterior capsule opacification prevention.

Clinical Translation of Long-Acting Drug Delivery Systems for Posterior Capsule Opacification Prophylaxis.

Posterior capsule opacification (PCO) remains the most common cause of vision loss post cataract surgery. The clinical management of PCO formation is limited to either physical impedance of residual lens epithelial cells (LECs) by implantation of specially designed intraocular lenses (IOL) or laser ablation of the opaque posterior capsular tissues; however, these strategies cannot fully eradicate PCO and are associated with other ocular complications. In this review, we critically appraise recent advances in conventional and nanotechnology-based drug delivery approaches to PCO prophylaxis. We focus on long-acting dosage forms, including drug-eluting IOL, injectable hydrogels, nanoparticles and implants, highlighting analysis of their controlled drug-release properties (e.g., release duration, maximum drug release, drug-release half-life). The rational design of drug delivery systems by considering the intraocular environment, issues of initial burst release, drug loading content, delivery of drug combination and long-term ocular safety holds promise for the development of safe and effective pharmacological applications in anti-PCO therapies.

HNF4A Negatively Regulated Posterior Capsular Opacification via Transcriptional Inhibition of MMP2

Purpose Posterior capsular opacification is the most common complication after cataract surgery. Abnormal proliferation, migration, epithelial-mesenchymal transition, and extracellular matrix synthesis of residual lens epithelial cells are considered to be the main pathogenic mechanisms. Hepatocyte nuclear factor 4α has been reported to regulate epithelial-mesenchymal transition in different tumors. Our objective was to investigate the role and mechanism of hepatocyte nuclear factor 4α in posterior capsular opacification. Methods Hepatocyte nuclear factor 4α expression was tested in posterior capsular opacification rat lens capsules and cell models. Hepatocyte nuclear factor 4α was knocked down using small hairpin RNA. Cell viability was measured by Cell Counting Kit-8 assay. Cell migration ability was evaluated by wound healing and Transwell assays. Epithelial-mesenchymal transition markers were detected by Western blotting. Transcriptome sequencing was used to screen for downstream effectors of hepatocyte nuclear factor 4α. Chromatin immunoprecipitation and a dual luciferase reporter assay were used to determine the binding of hepatocyte nuclear factor 4α to the MMP2 promoter region. Results Hepatocyte nuclear factor 4α was downregulated in posterior capsular opacification tissue and cell models. In vitro studies showed that hepatocyte nuclear factor 4α deletion facilitated cell proliferation, migration, and epithelial-mesenchymal transition protein marker expression in lens epithelial cells. Hepatocyte nuclear factor 4α knockdown promoted epithelial-mesenchymal transition and migration of lens epithelial cells via MMP2. Mechanistically, hepatocyte nuclear factor 4α decreased MMP2 expression by binding to the MMP2 promoter region. Hepatocyte nuclear factor 4α deletion also promoted epithelial-mesenchymal transition in rat lens capsules. Conclusions We demonstrated that hepatocyte nuclear factor 4α inhibited epithelial-mesenchymal transition of lens epithelial cells by directly binding to the MMP2 promoter region and inhibiting the expression of MMP2, thus leading to retardation of posterior capsular opacification formation and development, suggesting that hepatocyte nuclear factor 4α is a potential therapeutic target for posterior capsular opacification.

Extracellular HSP90 promotes differentiation of lens epithelial cells to fiber cells by activating LRP1-YAP-PROX1 axis.

Capsular residual lens epithelial cells (CRLEC) undergo differentiation to fiber cells for lens regeneration or tansdifferentiation to myofibroblasts leading to posterior capsular opacification (PCO) after cataract surgery. The underlying regulatory mechanism remains unclear. Using human lens epithelial cell lines and the ex vivo cultured rat lens capsular bag model, we found that the lens epithelial cells secrete HSP90α extracellularly (eHSP90) through an autophagy-associated pathway. Administration of recombinant GST-HSP90α protein or its M-domain induces the elongation of rat CRLEC cells with concomitant upregulation of the crucial fiber cell transcriptional factor PROX1and its downstream targets, β- and γ-crystallins and structure proteins. This regulation is abolished by PROX1 siRNA. GST-HSP90α upregulates PROX1 by binding to LRP1 and activating LRP1-AKT mediated YAP degradation. The upregulation of GST-HSP90α on PROX1 expression and CRLEC cell elongation is inhibited by LRP1 and AKT inhibitors, but activated by YAP-1 inhibitor (VP). These data demonstrated that the capsular residue epithelial cells upregulate and secrete eHSP90α, which in turn drive the differentiation of lens epithelial cell to fiber cells. The recombinant HSP90α protein is a potential novel differentiation regulator during lens regeneration.

Non-viral gene coating modified IOL delivering PDGFR-α shRNA interferes with the fibrogenic process to prevent posterior capsular opacification.

Posterior capsule opacification (PCO), the most common complication after cataract surgery, is caused by the proliferation, migration and epithelial-mesenchymal transition (EMT) of residual lens epithelial cells in the capsule bag. Although the surface modification and drug loading of intraocular lens (IOLs) have been effective in preventing PCO to some extent, the intraocular safety of anti-proliferative drug application is still a major limitation in clinical application. In this study, we used non-viral gene delivery systems in combination with layer-by-layer (LBL) self-assembly technology, and the modified IOL could effectively prevent the development of PCO by interfering with the EMT process mediated by the platelet-derived growth factor receptor-α (PDGFR-α). Herein, the gene fragments were wrapped by electrostatic conjugation using polyethyleneimine-graft-poly(ethylene glycol) to form gene complexes. Gene complexes were characterized by dynamic light scattering, transmission electron microscopy (TEM) and agarose gel electrophoresis, and evaluated for storage and serum stability. The layer assembly behavior of the IOL surface, changes in optical properties and the release behavior of the gene complexes were characterized using quartz crystal microbalance, UV-vis, contact angle and TEM. In vitro experiments showed that the IOL coating has good bio-compatibility and can achieve the corresponding transfection effect, and the released gene complexes exhibited excellent cell internalization and lysosomal escape behaviors, as well as effective inhibition of PDGFR-α expression and its mediated EMT process. The early PCO prevention effect and bio-compatibility evaluation of the modified IOL in vivo were evaluated by implantation into animal eyes. This study provides a new strategy for the development of surface modifications of small nucleic acid drugs and non-toxic EMT interference therapies for PCO.

Astragaloside IV inhibits the proliferation and migration of lens epithelial cells induced by TGF-β through the Jagged-1/Notch pathway

Aberrant proliferation and migration of residual lens epithelial cells (LECs) is the main cause of posterior capsule opacification (PCO) after cataract surgery. The purpose of this study was to confirm the protective effects of Astragaloside IV (AST) in transforming growth factor beta (TGF-β)-induced proliferation and migration of LECs. Human LECs, SRA01/04, were used in this study. MTT assay and EdU assay were used to perform cell viability and proliferation, respectively. The cell cycle was determined using flow cytometry. Cell invasion and migration were determined using transwell assay and wound healing assay, respectively. Protein expression was examined using western blotting. Type I and IV collagen (Col I and IV) and fibronectin (FN) in cells were also detected using immunofluorescence (IF). Cell viability, proliferation, migration and invasion were suppressed by AST in a concentration-dependent manner in TGF-β-treated LECs. AST stopped the cell cycle at G2 phase in a concentration-dependent manner. Expression of Cyclin B1 and CDK1 was suppressed by AST in TGF-β-treated LECs. Protein expression of FN, Col I, Col IV, α-SMA (α-smooth muscle actin), Snail and Slug was downregulated by AST in a concentration-dependent manner. AST inhibited the protein expression of Jagged-1, Notch1, Notch2, Notch3, Hes-1 and Hey-1. Taken together, data from this study demonstrated that AST inhibited LEC viability, proliferation, migration and invasion, as well as fibroblastic differentiation and epithelial-mesenchymal transition process through inhibition of Jagged-1/Notch pathway, providing a potential supplemental treatment for PCO.

“NIR-triggered ROS storage” photodynamic intraocular implant for high-efficient and safe posterior capsular opacification prevention

Posterior capsular opacification (PCO) is the leading cause of vision loss after cataract, mainly caused by the adhesion, proliferation and trans-differentiation of post-operative residual lens epithelial cells (LECs). Effective PCO prevention remains a huge challenge to ophthalmologists and researches for decades. Herein, we developed a “NIR-triggered ROS storage” intraocular implant (CTR-Py-PpIX) based on capsular tension ring (CTR), which is concurrently linked with photosensitizer protophorphyrin IX (PpIX) and energy storage 2-pyridone derivative (Py), to guarantee instantaneous and sustainable ROS generation for LECs killing, aiming to achieve more efficient and safer photodynamic therapy (PDT) to effectively prevent PCO. The silylated PpIX-Si and Py-Si were covalently conjugated to the plasma activated CTR surface to obtain CTR-Py-PpIX. Results demonstrated that CTR-Py-PpIX had dual functions of PDT and battery, in which PpIX could generate ROS extracellularly under irradiation, with one part directly inhibiting LECs by lipid peroxidation (LPO) induction of cell membranes. Meanwhile, the excess ROS stored in Py could be continuously released to amplify LPO levels after the irradiation was removed. Ultimately, the proliferation of LECs in capsular bag was completely inhibited under mild irradiation conditions, achieving a sustainable and controlled PDT effect for effective PCO prevention with good biocompatibility. This NIR-triggered ROS storage intraocular implant would provide a more efficient and safer approach for long-term PCO prevention.

Positive resolution of the wound-healing response in lens epithelial cells by Ti3C2T x MXene coatings for use in accommodative intraocular lens devices

Cataract surgery removes the diseased lens of the eye replacing it with an intraocular lens, restoring visual acuity. However, accommodation, the lens’ ability to provide dynamic change in focus, is lost. A number of accommodative intraocular lens (AIOL) designs have been considered although none have provided a truly effective clinical AIOL. Two-dimensional titanium carbide (Ti3C2T x ) MXene has been used as a transparent conductive electrode within an AIOL feasibility study. Nevertheless, the potential for Ti3C2T x to repress excessive inflammation and promote wound healing following cataract surgery has not been considered. Cataract surgery can trigger chronic inflammation and epithelial-mesenchymal transition (EMT) in residual lens epithelial cells (LECs), producing a fibrotic mass across the posterior capsule known as posterior capsule opacification (PCO). With a large surface area and capacity for surface functionalisation, MXene has properties enabling a dual purpose AIOL design with an additional therapeutic role in the repression of pathways leading to PCO development. In this study, Ti3C2T x MXene was investigated to determine its impact on pathways leading to chronic inflammation and EMT using an in vitro LECs model. Ti3C2T x MXene was synthesised and characterised using UV-vis spectroscopy, dynamic light scattering and scanning electron microscopy. Changes in markers linked to inflammation and EMT in Ti3C2T x -treated LECs were measured using enzyme linked immunosorbent assays, quantitative polymerase chain reaction, scratch assay, RNA sequencing for whole-cell gene expression profiling and lipidomics analysis. Ti3C2T x significantly reduced the expression of pro-inflammatory cytokines by interleukin 1 beta primed LECs and did not advocate EMT, promoting a positive resolution of the wound healing response. This study supports the role of Ti3C2T x within an AIOL design with the potential to repress key developmental pathways leading to PCO.