Prevention Of Posterior Capsular Opacification Research Articles

Overexpression of TRPV1 activates autophagy in human lens epithelial cells under hyperosmotic stress through Ca2+-dependent AMPK/mTOR pathway.

To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells (LECs) under hyperosmotic stress. LECs were treated with hyperosmotic stress at the concentration of 270, 300, 400, 500, or 600 mOsm for 6, 12, 18, 24h in vitro. Polymerase chain reaction (PCR) was employed for the mRNA expression of autophagy-related genes, while Western blotting detected the targeted protein expression. The transfection of stub-RFP-sens-GFP-LC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux. Scanning electron microscopy was used to detect the existence of autolysosome. Short interfering RNA of autophagy-related gene (ATG) 7, transient receptor potential vanilloid (TRPV) 1 overexpression plasmid, related agonists and inhibitors were employed to their influence on autophagy related pathway. Flow cytometry was employed to test the apoptosis and intracellular Ca2+ level. Mitochondrial membrane potential was measured by JC-1 staining. The cell counting kit-8 assay was used to calculate the cellular viability. The wound healing assay was used to evaluate the wound closure rate. GraphPad 6.0 software was utilized to evaluate the data. The hyperosmotic stress activated autophagy in a pressure- and time-dependent manner in LECs. Beclin 1 protein expression and conversion of LC3B II to LC3B I increased, whereas sequestosome-1 (SQSTM1) protein expression decreased. Transient Ca2+ influx was stimulated caused by hyperosmotic stress, levels of mammalian target of rapamycin (mTOR) phosphorylation decreased, and the level of AMP-activated protein kinase (AMPK) phosphorylation increased in the early stage. Based on this evidence, autophagy activation through the Ca2+-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress. Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased. Inhibition of autophagy by ATG7 knockdown had similar results. TRPV1 overexpression increased autophagy and might be crucial in the occurrence of autophagy promoted by hyperosmotic stress. A combination of hyperosmotic stress and autophagy inhibition may be a promising approach to decrease the number of LECs in the capsular bag and pave the way for improving prevention of posterior capsular opacification and capsular fibrosis.

Photo-controllable drug releasing bulk polyacrylic intraocular lens material for safer posterior capsular opacification prevention

Posterior capsular opacification (PCO) is the most common complication that occurs after intraocular lens (IOL) implantation in cataract therapy. In recent years, IOLs have been developed as drug delivery platforms, but concerns over the safety of uncontrolled proliferative drug release have arisen. Therefore, a controlled drug release strategy is needed for safer PCO prevention. In this study, a new monomer contained coumarin group was introduced in material preparation, and poly(ethylene glycol phenyl ether methacrylate-co-2-(2-ethoxyethoxy) ethyl acrylate-co-7-(2-methacryloyloxyethoxy)-4-methylcoumarin) (PEEC) acrylic IOL materials were synthesized. The antiproliferative drug 5-fluorouracil (5-FU) could be chemically grafted to the PEEC IOL materials easily via a light induced [2 + 2] cycloaddition reaction with the coumarin group, getting drug-loaded IOL (PEEC@5-FU IOL). The PEEC@5-FU IOL exhibited excellent optical and mechanical properties and biocompatibility. More importantly, the loaded 5-FU could be easily controlled from release by light irradiation via photo-dissociation of the cyclobutane ring that was obtained by the [2 + 2] cycloaddition reaction of 5-FU and coumarin. The in vitro and in vivo experiments demonstrated that such photo-controllable drug release IOL could effectively prevent PCO after implantation in a safe way.

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.

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.

Blue light attenuates TGF-β2-induced epithelial-mesenchymal transition in human lens epithelial cells via autophagy impairment

BackgroundPathogenesis of posterior capsular opacification (PCO) was related to pathological epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs). It has been reported that blue light could have an effect on EMT. This study aims to elucidate the role and potential mechanism of autophagy in EMT after blue light exposure in LECs.MethodsHLE-B3 cells were treated with TGF-β2 with different concentration and time to induce EMT as a model of PCO in vitro. Cells were exposed to blue light with or without TGF-β2. The expression levels of EMT-associated markers were analyzed by qRT-PCR, western blotting and cell migration ability was determined by transwell migration assay and wound healing assay. The expressions of autophagy-related proteins were analyzed by western blotting, immunofluorescence and transmission electron microscopy. Rapamycin and chloroquine were utilized in cells for autophagy activation and inhibition.ResultsTGF-β2 induced autophagy activation during EMT progression in HLE-B3 cells in a dose- and time-dependent manner. Blue light exposure inhibited TGF-β2-induced EMT characterized by inhibited expression of EMT related markers and reduced migration capacity. Meanwhile, blue light exposure impaired autophagy activated by TGF-β2. Furthermore, Autophagy activation with rapamycin rescued EMT attenuated by blue light. Autophagy inhibition with chloroquine reduced TGF-β2-induced EMT in HLE-B3 cells.ConclusionBlue light exposure had inhibited effects on TGF-β2-induced EMT in LECs through autophagy impairment, which provides a new insight on prevention and treatment of 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.

Spin-Coating-Based Facile Annular Photodynamic Intraocular Lens Fabrication for Efficient and Safer Posterior Capsular Opacification Prevention.

Posterior capsular opacification (PCO) is the most common complication after cataract surgery, which is primarily caused by the proliferation of the residual lens epithelial cells (LECs) in the lens capsule. Previous studies have demonstrated that a drug-eluting intraocular lens (IOL), aimed to in situ eliminate LECs, are an effective and promising way to prevent PCO. However, because of the potential toxicities of the antiproliferative drugs to the adjacent tissues, the safety of such drug-eluting IOLs is still a highly important issue to be solved. In this investigation, a facile photodynamic coating-modified IOL was developed for effective and safer PCO prevention. An annular poly(lactide-co-glycolic acid) (PLGA) coating loaded with photosensitizer chlorin e6 (Ce6) was prepared by a spin-coating technique. The optical property investigations showed that the Ce6@PLGA coating was particularly suitable for the IOL surface modification. The in vitro cell culture investigation showed that Ce6@PLGA coating-modified IOLs effectively eliminated LECs when treated with light illumination, whereas it appeared to have good cytocompatibility without irradiation. The investigation of the cell elimination mechanism showed that the apoptosis of HLECs may be associated with the cytomembrane disruption induced by ROS, which is generated by the photodynamic coating during light illumination. The in vivo implantation experiments confirmed the desired PCO prevention effect, as well as the safety to and biocompatibility with the surrounding tissues. Thus, the facile Ce6@PLGA coating will provide an effective yet safe alternative of IOL surface modification for PCO prevention.

Rapid and Economical Drug-Eluting IOL Preparation via Thermoresponsive Agarose Coating for Effective Posterior Capsular Opacification Prevention.

Posterior capsular opacification (PCO), the highest incidence complication after cataract surgery, is mainly due to the attachment, proliferation, and migration of the residual lens epithelial cells (LECs). Although the drug-eluting IOLs have been proved to be an effective way to prevent PCO incidence, its preparations are time consuming and require tedious preparation steps. Herein, the thermoreversible agarose is adopted to prepare drug-eluting IOL. Such functional coating can be obtained easily by simple immersion in the antiproliferative drug containing hot agarose and taken out for cooling, which not only does not affect the optical property but also can effectively decrease the PCO incidence after intraocular implantation. As a result, the proposed agarose coating provides a rapid and economical alternative of drug-eluting IOL fabrication for PCO prevention.

IGF-1 Promotes Epithelial-Mesenchymal Transition of Lens Epithelial Cells That Is Conferred by miR-3666 Loss.

The abnormal proliferation, migration, and epithelial-mesenchymal transformation (EMT) of lens epithelial cells (LECs) are the main reasons for vision loss caused by posterior capsular opacification (PCO) after cataract surgery. Insulin-like growth factor-1 (IGF-1) was found to be associated with the pathogenesis of cataracts, but its biological role in PCO is poorly understood. In the present study, IGF-1 overexpression facilitated the proliferation, migration, and EMT, whereas knockdown of IGF-1 markedly suppressed the proliferation, migration, and TGF-β2-induced EMT of LECs. Additionally, to evaluate valuable microRNAs (miRNAs) which target IGF-1 to modulate LEC-EMT, we predicted miR-3666 might regulate IGF-1 by binding its 3'UTR according to the bioinformatics database. Furthermore, we verified that miR-3666 directly targeted IGF-1 by luciferase reporter assay. By using miR-3666 mimics, cell proliferation, migration, and invasion were suppressed, while being enhanced by the reduction of miR-3666. Knockout of IGF1 reverses the effect of the miR-3666 inhibitor on the malignant behavior of LECs. These results indicate the role of miR-3666/IGF-1 in LEC-EMT that offers new strategies for the therapy and prevention of PCO.

Nanoporous Gold Ring-Integrated Photothermal Intraocular Lens for Active Prevention of Posterior Capsular Opacification.

Posterior capsular opacification (PCO) is the leading complication after cataract surgery, and is mainly induced by the proliferation and migration of residual lens epithelial cells (LECs). Although numerous attempts have been made to reduce the incidence of PCO, this complication remains a critical challenge in postoperative visual recovery. This study aims to report a functionalized intraocular lens (R-IOL) with a region-confined photothermal effect for the active prevention of PCO after implantation. The outer rim of R-IOL (non-optical area) is decorated with a nanoporous gold (NPG) ring, which can effectively eliminate the LECs around R-IOL, ultimately inhibiting the migration of LECs from the periphery to the visual axis center in the initial stage, and preventing the subsequent PCO. Furthermore, the mechanism of LECs elimination can be attributed to apoptosis induced by mild photothermal therapy. After in vivo implantation for 30 days, PCO is rarely observed in the R-IOL group, whereas the considerably higher incidence of PCO (75%) is found in the pristine IOL (P-IOL) group. The region-confined photothermal effect based on NPG not only provides an active strategy to effectively prevent PCO, but also introduces new opportunities for the treatment of undesirable hyperplasia.

Thin film nanoarchitectonics of layer-by-layer assembly with reduced graphene oxide on intraocular lens for photothermal therapy of posterior capsular opacification

Due to development of surgical techniques and intraocular lens (IOL) implants, vision can often be restored in cataracts patients. However, posterior capsular opacification (PCO) has become the most common and challenging complication in cataracts surgery. While various approaches such as surface modification and drug prophylaxis have been investigated to prevent PCO development, there is no standard treatment that is sufficiently safe and effective to meet clinical demands. Near-infrared (NIR) light-triggered photothermal therapy is an attractive noninvasive treatment for PCO prophylaxis. We fabricated a new type of IOL with excellent biocompatibility, stability, and photothermal conversion property. Polyethyleneimine (PEI) and graphene oxide (GO) were layer-by-layer assembled on model polymethylmethacrylate and IOL substrates, and the thickness, surface roughness, and wettability of the substrates with different numbers of bilayers were evaluated. After the reduction of GO to reduced GO (rGO), a rGO/PEI multilayer thin film with good stability and photothermal conversion capability was obtained. The rGO/PEI multilayer coating was able to induce apoptosis in lens epithelium cells under 808-nm NIR laser irradiation in vitro. Finally, rGO@IOL was implanted into rabbit eyes, and the biocompatibility and ability to prevent PCO were evaluated for 5 weeks. The rGO@IOL implant exhibited excellent PCO prevention ability with the assistance of NIR irradiation and did not induce obvious pathological effects in surrounding healthy tissues. The rGO@IOL implant with good biocompatibility, good physicochemical stability, and excellent photothermal conversion property shows promise for clinical application in PCO prophylaxis.

Foldable Bulk Anti-adhesive Polyacrylic Intraocular Lens Material Design and Fabrication for Posterior Capsule Opacification Prevention.

Posterior capsular opacification (PCO) is a primary complication after phacoemulsification combined with intraocular lens (IOL) implantation, which is attributed to adhesion, proliferation, and migration of residual lens epithelial cells on IOL. Although surface hydrophilic coating is considered to be a powerful way to inhibit PCO incidence after surgery, it requires complex post-production processes, thus limiting their applicability. In comparison, bulk modification is a stable, effective, and facile IOL synthesis method for PCO prevention. Herein, a new anti-adhesive IOL material was designed and successfully synthesized by radical copolymerization of ethylene glycol phenyl ether methacrylate (EGPEMA) and 2-(2-ethoxyethoxy) ethyl acrylate (EA). The physicochemical properties of P(EGPEMA-co-EA) copolymer materials, including chemical structure, mechanical, thermal, surface, and optical properties, were analyzed by using 1H NMR spectroscopy, FT-IR spectroscopy, tensile test, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), water contact angle measurement, and UV-vis spectroscopy. The elongation at break and the modulus of elasticity of the copolymer were tunable through the change of the composition of monomers. Compared to other components, the tensile results showed that P(EGPEMA-co-EA) materials (70% EGPEMA in mass ratio, F7) are suitable for the preparation of foldable intraocular lens with lower elastic modulus and higher elongation at break. TGA and DSC showed that the material has high thermal stability, and the glass transition temperature of F7 material is 16.1 °C. The water contact angle measurement results showed that the introduction of EA improved the hydrophilicity of the material. The percentage of transmittance of all copolymers at 400-800 nm is above 85%. Then, the biocompatibility of the materials was evaluated by in vitro assay and subcutaneous implantation. Both in vitro results and subcutaneous implantation experiments showed that the designed IOL materials exhibited a good anti-adhesion effect and no cytotoxicity. Finally, phacoemulsification and IOL intraocular implantation were performed, and the in vivo results confirmed the good PCO prevention ability as well as the biocompatibility of the new IOL materials.

Augmented cellular uptake and homologous targeting of exosome-based drug loaded IOL for posterior capsular opacification prevention and biosafety improvement.

Posterior capsular opacification (PCO), the most common complication after cataract surgery, is caused by the proliferation, migration and differentiation of residual lens epithelial cells (LECs) on the surface of the intraocular lens (IOL). Although drug-loaded IOLs have been successfully developed, the PCO prevention efficacy is still limited due to the lack of targeting and low bioavailability. In this investigation, an exosome-functionalized drug-loaded IOL was successfully developed for effective PCO prevention utilizing the homologous targeting and high biocompatibility of exosome. The exosomes derived from LECs were collected to load the anti-proliferative drug doxorubicin (Dox) through electroporation and then immobilized on the aminated IOLs surface through electrostatic interaction. In vitro experiments showed that significantly improved cellular uptake of Dox@Exos by LECs was achieved due to the targeting ability of exosome, compared with free Dox, thus resulting in superior anti-proliferation effect. In vivo animal investigations indicated that Dox@Exos-IOLs effectively inhibited the development of PCO and showed excellent intraocular biocompatibility. We believe that this work will provide a targeting strategy for PCO prevention through exosome-functionalized IOL.

Centrifugally concentric ring-patterned drug-loaded polymeric coating as an intraocular lens surface modification for efficient prevention of posterior capsular opacification

Posterior capsular opacification (PCO) is the main postoperative complication after intraocular lens (IOL) implantation in cataract surgery, because of the proliferation of the residual lens epithelial cells (LECs) in the lens capsule. Drug-eluting IOLs, aimed to develop an in situ drug delivery device, are the promising concept in recent years. As IOLs are optical devices other than implants, the feasibility and applicability remain a challenge for drug-eluting coatings. In this investigation, a centrifugally concentric ring-patterned drug-loaded poly(lactide-co-glycolic acid) (PLGA) coating was designed and fabricated by the spin coating technique. The concentric ring-patterned morphologies and the drug loading and release properties were carefully investigated, and the spin coating parameters were optimized. A concentric annular coating with a thin center and thick periphery was obtained, which was particularly suitable for the surface modification of IOLs, as the visual pathway of the intraocular light transmission greatly requires good light transmittance of the IOLs. IOLs with the immunosuppressant cyclosporin A (CsA)-loaded coating (CsA @ PLGA) modification were then fabricated for PCO prevention. The in vitro LECs culture results showed that the CsA @ PLGA coating-modified IOLs significantly inhibited cell proliferation and induced cell death. Western blot analysis showed that the efficient cell inhibition behavior of CsA was due to the autophagy-mediated cell death pathway. The in vivo intraocular implantation results confirmed the desired PCO inhibition effect. Thus, the centrifugally concentric ring-patterned drug-loaded PLGA coating obtained by the spin coating technique provides a simple yet effective alternative of IOL modification for PCO prevention. Statement of Significance• Concentric ring-patterned polymer coating, specifically for drug-eluting IOL fabrication, was developed by the spin coating technique.• The immunosuppressant CsA inhibited LEC proliferation through the autophagy-mediated cell death pathway.• Concentric ring-patterned CsA-eluting IOLs exhibited reliable in vivo PCO prevention.• The drug-eluting IOLs fabricated by the simple and economical spin coating technique have a great potential in clinical translation.

αVβ8 integrin targeting to prevent posterior capsular opacification.

Fibrotic posterior capsular opacification (PCO), a major complication of cataract surgery, is driven by transforming growth factor–β (TGF-β). Previously, αV integrins were found to be critical for the onset of TGF-β–mediated PCO in vivo; however, the functional heterodimer was unknown. Here, β8 integrin–conditional knockout (β8ITG-cKO) lens epithelial cells (LCs) attenuated their fibrotic responses, while both β5 and β6 integrin–null LCs underwent fibrotic changes similar to WT at 5 days post cataract surgery (PCS). RNA-Seq revealed that β8ITG-cKO LCs attenuated their upregulation of integrins and their ligands, as well as known targets of TGF-β–induced signaling, at 24 hours PCS. Treatment of β8ITG-cKO eyes with active TGF-β1 at the time of surgery rescued the fibrotic response. Treatment of WT mice with an anti-αVβ8 integrin function blocking antibody at the time of surgery ameliorated both canonical TGF-β signaling and LC fibrotic response PCS, and treatment at 5 days PCS, after surgically induced fibrotic responses were established, largely reversed this fibrotic response. These data suggest that αVβ8 integrin is a major regulator of TGF-β activation by LCs PCS and that therapeutics targeting αVβ8 integrin could be effective for fibrotic PCO prevention and treatment.

Photo-responsive intraocular lens with on demand drug release for posterior capsule opacification prevention and improved biosafety

Posterior capsular opacification (PCO) is the most common complication after cataract surgery, which is caused by the adhesion, proliferation, migration and epithelial-mesenchymal transformation of the residual lens epithelial cells (LECs) in lens capsule. The drug eluting coating modification provides a powerful way to inhibit PCO incidence after IOL implantation. However, the uncontrolled proliferative drug brings intraocular biosafety issues when application. Therefore, developing new strategies with controlled drug release for PCO prevention is of great significance. In this investigation, a hydrophilic photo-responsive drug release coating was successfully constructed on IOL surface, which was verified through 1H•NMR, UV–Vis, FTIR and XPS. In vitro assay indicated that the IOL coating exhibited excellent anti-adhesion and anti-proliferation effects on LECs under irradiation. The photo-controlled drug release in vitro can be achieved by simply adjusting the intensity and time of irradiation. Finally, the surface-modified IOL was implanted in rabbit eyes and in vivo evaluation was carried out. In vivo assay demonstrated that the implantation of the modified IOL into eyes can significantly reduce the occurrence of PCO. Moreover, the modified IOL exhibited good biocompatibility and biosafety. We believe that this work will provide a synergistic strategy for effective prevention of PCO through a photo-controllable drug release coating on IOL surface.

Drug-eluting intraocular lens with sustained bromfenac release for conquering posterior capsular opacification

Cataract is the leading cause of visual impairment, and posterior capsular opacification (PCO) is the most common long-term complication of modern cataract surgery, which can cause severe visual impairment after surgery. The proliferation, migration, and epithelial-mesenchymal transition (EMT) of residual lens epithelial cells (LECs) stimulated by growth factors and cytokines, are the key pathological mechanisms involved in the development of PCO. This study demonstrated that non-steroidal anti-inflammatory drug (NSAID), bromfenac, was capable of effectively inhibiting cell migration, overexpression of EMT markers, such as fibronectin (FN), matrix metalloproteinase 2 (MMP2), α-smooth muscle actin (α-SMA), and transcription factor Snail, and extracellular signal-regulated kinase (ERK)/glycogen synthase kinase-3β (GSK-3β) signaling induced by transforming growth factor-β2 (TGF-β2) in vitro. The inhibitory effect of bromfenac on TGF-β2-induced EMT was also verified on a primary lens epithelial cell model using human anterior capsules. Furthermore, based on ultrasonic spray technology, we developed a drug-eluting intraocular lens (IOL) using poly (lactic-co-glycolic acid) (PLGA) with sustained bromfenac release ability for the prevention of PCO development. In the rabbit models of cataract surgery, bromfenac-eluting IOL exhibited remarkable PCO prevention and inflammation suppression effects with excellent biocompatibility. In conclusion, bromfenac can inhibit TGF-β2-induced cell migration and the EMT of LECs via ERK/GSK-3β/Snail signaling. The present study offers a novel approach for preventing PCO through PLGA-based drug sustained-release IOLs.

Capsule polishing during cataract surgery: techniques and its role in preventing posterior capsular opacification

Posterior capsular opacification (PCO) is the most common complication that leads to vision loss after cataract surgery. It is classically divided into fibrotic type and regenerative type according to clinical manifestations or pathological mechanisms. The widely used technique for preventing PCO is to mechanically polish anterior and posterior capsules after an uneventful phacoemulsification surgery. However, the efficacy of polishing anterior capsules on prevention of PCO is debatable. It has been found that polishing anterior capsules has an inhibitory or no effect on fibrotic PCO, but a stimulating effect on regenerative PCO. Therefore, whether to polish anterior capsules is dependent on the condition of individual patients and the type of intraocular lenses. (Chin J Ophthalmol, 2021, 57: 492-494).

Drug-Eluting Hydrophilic Coating Modification of Intraocular Lens via Facile Dopamine Self-Polymerization for Posterior Capsular Opacification Prevention.

Posterior capsular opacification (PCO) is the most important complication in cataract phacoemulsification and intraocular lens (IOL) implantation surgery, mainly stemming from the adhesion, proliferation, and transdifferentiation of the postsurgically residual lens epithelial cells (LECs). Previous investigations mainly focused on the hydrophilic surface modification of the IOLs for PCO prevention, such as heparinization. However, the long-term clinical investigations show that there is no significant difference between pristine and heparinized IOLs. In the present study, a synergetic coating with properties of drug-eluting and hydrophilicity was designed and modified onto the IOL surface via facile dopamine self-polymerization. The antiproliferative drug doxorubicin (DOX) was loaded when a polydopamine (PDA) coating was formed on the IOL surface. The hydrophilic 2-methacryloyloxyethyl phosphorylcholine (MPC) could be subsequently grafted onto the drug-loaded PDA coating surface easily. The hydrophilic outer layer could slow down drug-eluting from underneath the drug-incorporated coating. In vitro and in vivo investigations demonstrated that such multifunctionalized coating-modified IOLs could not only thoroughly and effectively prevent PCO development by induced cell apoptosis but also render safety and biocompatibility to the surrounding tissues.

Enhanced PCO prevention of drug eluting IOLs via endocytosis and autophagy effects of a PAMAM dendrimer.

Drug-loaded intraocular lenses (IOLs) have received considerable attention in treating complications that arise after cataract surgery, especially posterior capsular opacification (PCO). However, for a better therapeutic effect, the drug concentration in IOLs usually needs to be increased. Herein, we developed multilayer (doxorubicin (DOX)@polyaminoamide (PAMAM) (D@P)/heparin sodium (HEP))5 modified IOLs, which efficiently enhance the inhibitory effect on PCO using the enhanced autophagy effect of a cationic PAMAM. The chemotherapeutic drug DOX was encapsulated in PAMAM to formulate cationic DOX@PAMAM nanoparticles. Subsequently, negatively charged HEP and D@P nanoparticles (NPs) were assembled on the aminated artificial IOL surface using the layer-by-layer (LBL) assembly technique. The (D@P/HEP)5 IOLs were implanted into rabbit eyes to evaluate the prevention of PCO. In vitro and in vivo research studies showed that the D@P NPs exhibited enhanced cellular uptake owing to the cell-penetrating cationic characteristics, while demonstrating enhanced autophagy. D@P NPs are more effective at the same DOX concentration when compared to free DOX. Multilayer-modified (D@P/HEP)5 IOLs can efficiently inhibit PCO after cataract surgery. This study provides a strategy for improving the therapeutic effect of antiproliferative drug DOX by using a cationic dendrimer, which, in turn, increases the level of autophagy of cells. These LBL-based multilayer IOLs have broad application prospects in the treatment of complications after cataract surgery.