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Cataract patients look forwards to fewer postoperative complications and higher vision quality after surgery. However, the current intraocular lens (IOL) implanted after cataract surgery neither can adjust focal length in response to ciliary muscle contraction as natural lens nor have the ability to prevent postoperative complications. Herein, a thermosensitve Poloxamer based hybrid hydrogel with antibacterial anti-inflammatory and photothermal functional elements doping was designed and used as injectable, in situ curable, and adjustable IOL (FHTAB IOL). The FHTAB IOL was composed of thermosensitve triblock-polymer F127DA and a small amount of HAMA, combined with BP NS, TA, and Ag NPs. FHTAB IOL can be injected into the empty lens capsule after cataract surgery via an injectable thermos-gel under NIR illumination and then be rapidly cured to form a full-size IOL under short-time blue light irradiation. The designed injectable FHTAB IOL possesses high transparency and transmittance, with a refractive index similar to the natural lens and adjustable properties. It was stabilized as a refractive medium without any leakage in the eye. In addition, the TA and Ag NPs loaded in the FHTAB IOL displayed significant antibacterial and anti-inflammatory effects in vitro and vivo. This study presents a potentially effective new strategy for the development of multifunctional adjustable IOLs.
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Dry eye disease (DED) is a chronic multifactorial ocular surface disease mainly caused by the instability of tear film, characterized by a series of ocular discomforts and even visual disorders. Oxidative stress has been recognized as an upstream factor in DED development. Diquafosol sodium (DQS) is an agonist of the P2Y2 receptor to restore the integrity/stability of the tear film. With the ability to alternate between Ce3+ and Ce4+, cerium oxide nanozymes could scavenge overexpressed reactive oxygen species (ROS). Hence, a DQS-loaded cerium oxide nanozyme was designed to boost the synergistic treatment of DED. Cerium oxide with branched polyethylenimine-graft-poly(ethylene glycol) as nucleating agent and dispersant was fabricated followed with DQS immobilization via a dynamic phenylborate ester bond, obtaining the DQS-loaded cerium oxide nanozyme (defined as Ce@PBD). Because of the ability to mimic the cascade processes of superoxide dismutase and catalase, Ce@PBD could scavenge excessive accumulated ROS, showing strong antioxidant and anti-inflammatory properties. Meanwhile, the P2Y2 receptors in the conjunctival cells could be stimulated by DQS in Ce@PBD, which can relieve the incompleteness and instability of the tear film. The animal experiments demonstrated that Ce@PBD significantly restored the defect of the corneal epithelium and increased the number of goblet cells, with the promotion of tear secretion, which was the best among commercial DQS ophthalmic solutions.
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Cério , Síndromes do Olho Seco , Cério/química , Cério/farmacologia , Animais , Síndromes do Olho Seco/tratamento farmacológico , Síndromes do Olho Seco/patologia , Síndromes do Olho Seco/metabolismo , Nucleotídeos de Uracila/química , Nucleotídeos de Uracila/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Humanos , Antioxidantes/química , Antioxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Polifosfatos/química , Polifosfatos/farmacologia , Camundongos , CoelhosRESUMO
Proliferative vitreoretinopathy (PVR) is a common cause of vision loss after retinal reattachment surgery and ocular trauma. The key pathogenic mechanisms of PVR development include the proliferation, migration and epithelial-mesenchymal transition (EMT) of retinal pigment epithelial cells (RPEs) activated by the growth factors and cytokines after surgery. Although some drugs have been tried in PVR treatments as basic investigations, the limited efficacy remains an obstacle, which may be due to the single pharmacological action and lack of targeting. Herein, the anti-proliferative Daunorubicin and anti-inflammatory Dexamethasone were co-loaded in the RPEs-derived exosomes (Exos), obtaining an Exos-based dual drug-loaded nanocarrier (Exos@D-D), and used for multiple PVR therapy. Owing to the advantages of homologous Exos and the dual drug loading, Exos@D-D showed good RPEs targeting as well as improved uptake efficiency, and could inhibit the proliferation, migration, as well as EMT of RPEs effectively. The animal studies have also demonstrated that Exos@D-D effectively inhibits the production of proliferative membranes and prevents the further development of inflammation, shows significant therapeutic effects on PVR and good biocompatibility. Such Exos-based dual drug-loaded nanocarrier investigation not only provides a promising approach for multifunctional exosome drug delivery systems construction, but also has great potential in PVR clinical therapy application.
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Dry eye disease (DED) is a kind of multifactorial ocular surface disease that displays ocular discomfort, visual disturbance, and tear film instability. Oxidative stress is a fundamental pathogenesis in DED. An imbalance between the reactive oxygen species (ROS) level and protective enzyme action will lead to oxidative stress, cell dysfunction, tear hyperosmolarity, and inflammation. Herein, a multifunctional cerium oxide nanozyme with high ocular surface retention property was designed to neutralize over-accumulated ROS and restore redox balance. Cerium oxide nanozymes were fabricated via branched polyethylenimine-graft-poly (ethylene glycol) nucleation and dispersion, followed by phenylboronic acid (PBA) functionalization (defined as Ce@PB). Due to the dynamic chemical bonding formation between the PBA segment and the cis-diol groups in the mucin layer of the tear film, Ce@PB nanozymes possess good adhesive capability to the ocular surface, thus extending the drug's retention time. On the other hand, Ce@PB nanozymes could mimic the cascade processes of superoxide dismutase and catalase to maintain intracellular redox balance. In vitro and in vivo studies suggest that such multifunctional nanozymes possess good biocompatibility and hemocompatibility. More importantly, Ce@PB nanozymes treatment in the animal model could repair corneal epithelial defect, increase the number of goblet cells and promote tear secretion, thus achieving an effective treatment for DED. STATEMENT OF SIGNIFICANCE.
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The human cannot detect light with a wavelength exceeding 700 nm, primarily due to limitations in the physiological structure of the human eye. However, in certain specific scenarios, the ability to detect near-infrared (NIR) light proves to be extremely valuable. To attain this desired capability, NIR up conversion nanoparticles (UCNPs) were prepared and doped in the optical lens materials, aiming to obtain a NIR light "visible" optical lens. It is demonstrated that the doping of UCNPs in the optical lens materials does not significantly impact on their mechanical properties, optical properties, surface properties and it exhibits excellent biocompatibility in cell and animal experiments. More importantly, the UCNPs doping can convert NIR light into visible light within the material effectively and stably. The eyes can "see" the NIR light after wearing such UCNPs doped optical lens. Such NIR light visible optical lens could have great potential in actual applications.
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Raios Infravermelhos , Nanopartículas , Nanopartículas/química , Animais , Humanos , Camundongos , Lentes , Materiais Biocompatíveis/química , Propriedades de SuperfícieRESUMO
Myopia is a global public health issue. Rigid contact lenses (RCLs) are an effective way to correct or control myopia. However, bioadhesion issues remain one of the significant obstacles limiting its clinical application. Although enhancing hydrophilicity through various surface treatments can mitigate this problem, the duration of effectiveness is short-lived and the processing involved is complex and costly. Herein, an antiadhesive RCLs material was designed via 8-armed methacrylate-POSS (8MA-POSS), and poly(ethylene glycol) methacrylate (PEGMA) copolymerization with 3-[tris(trimethylsiloxy)silyl] propyl methacrylate (TRIS). The POSS and PEG segments incorporated P(TRIS-co-PEGMA-co-8MA-POSS) (PTPM) material was obtained and their optical transparency, refractive index, resolution, hardness, surface charge, thermal features, and wettability were tested and optimized. The antibioadhesion activities, including protein, lipid, and bacteria, were evaluated as well. In vitro and in vivo results indicated that the optimized antibioadhesive PTPM materials present good biocompatibility and biosafety. Thus, such POSS and PEG segments containing material were a potential antibioadhesive RCL material option.
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Lentes de Contato , Metacrilatos , Compostos de Organossilício , Polietilenoglicóis , Polietilenoglicóis/química , Metacrilatos/química , Animais , Compostos de Organossilício/química , Compostos de Organossilício/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Camundongos , Materiais Biocompatíveis/química , Humanos , Miopia/tratamento farmacológicoRESUMO
[This corrects the article DOI: 10.1039/C5RA08668J.].
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Expression of Concern for 'Surface modification of intraocular lenses via photodynamic coating for safe and effective PCO prevention' by Junmei Tang et al., J. Mater. Chem. B, 2021, 9, 1546-1556, https://doi.org/10.1039/D0TB02802A.
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Intraocular lens (IOL) implantation is currently the most effective clinical treatment for cataracts. Nevertheless, due to the growth of the eye axis in patients with congenital cataracts during the process of growth and development, the progressive incapacity of an IOL with a fixed focus does not meet the demands of practical usage, leading to the occurrence of ametropia. This work describes an innovative class of an IOL bulk material that offers good biosafety and light-controlled refractive index adjustment. Acrylate materials were synthesized for the preparation of IOLs by free radical polymerization of ethylene glycol phenyl ether methacrylate (EGPEMA), hydrophilic monomer 2-(2-ethoxyethoxy) ethyl acrylate (EA), and functional monomer hydroxymethyl coumarin methacrylate (CMA). Under 365/254 nm ultraviolet (UV) irradiation, the coumarin group could adjust the polymer material's refractive index through reversible photoinduced dimerization/depolymerization. Meanwhile, the potential for the IOL use is enabled by its satisfactory biosafety. Such a light-induced diopter adjustable IOL will be more appropriate for implantation during cataract surgery since it will not require the correction needed for ametropia and will offer more accurate and humane treatment. STATEMENT OF SIGNIFICANCE.
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Catarata , Lentes Intraoculares , Erros de Refração , Humanos , Implante de Lente Intraocular , Acuidade Visual , Refratometria , Cumarínicos , MetacrilatosRESUMO
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.
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Lentes Intraoculares , Metacrilatos , Polietilenoglicóis , Liberação Controlada de Fármacos , Fluoruracila , CumarínicosRESUMO
Posterior capsule opacification (PCO), as one of the most common late complications after intraocular lens (IOL) implantation in cataract surgery, seriously affects patients' postoperative vision and surgical satisfaction, and can only be treated by laser incision of the posterior capsule. Although drug eluting coating modification have been proved to inhibit PCO effectively, the complicated coating methods and the potential toxicity of the antiproliferative drugs hinders its actual application. In this study, an indocyanine green (ICG) loaded polydopamine (PDA) coating modified IOL (IP-IOL) was designed to prevented PCO. In vitro and in vivo studies have shown that IP-IOL can effectively eliminate lens epithelial cells and significantly reduce the degree of PCO. At the same time, it still has good imaging quality and optical properties. Furthermore, both the near-infrared irradiation and ICG loaded PDA coating modified IOLs have proved to possess high biological safety to eyes. Thus, with easy preparation and safer near-infrared irradiated photothermal/photodynamic synchronous properties, such ICG loaded PDA coating provides an effective yet easier and safer PCO prevention after IOL implantation.
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Opacificação da Cápsula , Lentes Intraoculares , Polímeros , Humanos , Opacificação da Cápsula/prevenção & controle , Olho Artificial , Indóis/uso terapêutico , Verde de Indocianina/uso terapêuticoRESUMO
Retraction of 'Construction of a temperature-responsive terpolymer coating with recyclable bactericidal and self-cleaning antimicrobial properties' by Bailiang Wang et al., Biomater. Sci., 2016, 4, 1731-1741, https://doi.org/10.1039/C6BM00587J.
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Expression of concern for 'In vitro and in vivo evaluation of xanthan gum-succinic anhydride hydrogels for the ionic strength-sensitive release of antibacterial agents' by Bailiang Wang et al., J. Mater. Chem. B, 2016, 4, 1853-1861, https://doi.org/10.1039/C5TB02046H.
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Posterior capsule opacification (PCO) is the most common complication after cataract surgery. Drug-eluting intraocular lens (IOLs) is a promising concept of PCO treatment in modern cataract surgery. However, the large dose of drugs in IOL leads to uncontrollable and unpredictable drug release, which inevitably brings risks of overtreatment and ocular toxicity. Herein, a low-power NIR-triggered thermosensitive IOL named IDG@P(NIPAM-co-AA)-IOL is proposed to improve security and prevent PCO by synergetic controlled drug therapy and simultaneous photo-therapy. Thermosensitive polymer brushes Poly(N-isopropylacrylamide-co-Acrylic acid) (P(NIPAM-co-AA)) is prepared on IOL via surface-initiated reversible addition-fragmentation chain transfer (SI-RAFT) polymerization. Then, Doxorubicin (DOX) and Indocyanine green (ICG) co-loaded Gelatin NPs (IDG NPs) are loaded in P(NIPAM-co-AA) by temperature control. The IDG NPs perform in suit photodynamic & photothermal therapy (PTT&PDT), and the produced heat also provides a trigger for controllable drug therapy with a cascade effect. Such functional IOL shows excellent synergistic drug-phototherapy effect and NIR-triggered drug release behavior. And there is no obvious PCO occurrence in IDG@P(NIPAM-co-AA) IOL under NIR irradiation compared with control group. This proposed IDG@P(NIPAM-co-AA)-IOL serves as a promising platform that combines phototherapy and drug-therapy to enhance the therapeutic potential and medication safety for future clinical application of PCO treatment.
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Opacificação da Cápsula , Lentes Intraoculares , Humanos , Opacificação da Cápsula/prevenção & controle , Fototerapia , Terapia Combinada , DoxorrubicinaRESUMO
Expression of concern for 'Synthesis of MA POSS-PMMA as an intraocular lens material with high light transmittance and good cytocompatibility' by Bailiang Wang et al., RSC Adv., 2014, 4, 52959-52966, https://doi.org/10.1039/C4RA08060B.
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As an acute ophthalmic infection, bacterial keratitis (BK) can lead to severe visual morbidity, such as corneal perforation, intraocular infection, and permanent corneal opacity, if rapid and effective treatments are not available. In addition to eradicating pathogenic bacteria, protecting corneal tissue from oxidative damage and promoting wound healing by relieving inflammation are equally critical for the efficient treatment of BK. Besides, it is very necessary to improve the bioavailability of drugs by enhancing the ocular surface adhesion and corneal permeability. In this investigation, therefore, a synergistic antibiotic-antioxidant treatment of BK was achieved based on multifunctional block copolymer vesicles, within which ciprofloxacin (CIP) was simultaneously encapsulated during the self-assembly. Due to the phenylboronic acid residues in the corona layer, these vesicles exhibited enhanced muco-adhesion, deep corneal epithelial penetration, and bacteria-targeting, which facilitated the drug delivery to corneal bacterial infection sites. Additionally, the abundant thioether moieties in the hydrophobic membrane enabled the vesicles to both have ROS-scavenging capacity and accelerated CIP release at the inflammatory corneal tissue. In vivo experiments on a mice model demonstrated that the multifunctional polymer vesicles achieved efficient treatment of BK, owing to the enhanced corneal adhesion and penetration, bacteria targeting, ROS-triggered CIP release, and the combined antioxidant-antibiotic therapy. This synergistic strategy holds great potential in the treatment of BK and other diseases associated with bacterial infections.
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Infecções Oculares Bacterianas , Ceratite , Animais , Camundongos , Antioxidantes/farmacologia , Polímeros/química , Espécies Reativas de Oxigênio , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ciprofloxacina , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/microbiologiaRESUMO
Fibrotic eye diseases, a series of severe oculopathy, that will destroy normal ocular refractive media and imaging structures. It is characterized by the transformation of the epithelial cells into mesenchyme cells. Proliferative vitreoretinopathy (PVR) is one of these representative diseases. In this investigation, polyethylene glycol grafted branched Polyethyleneimine (PEI-g-PEG) was used as a non-viral gene vector in gene therapy of PVR to achieve anti-fibroblastic effects in vitro and in vivo by interfering with platelet-derived growth factor alpha receptor (PDGFR-α) in the epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells. The plasmid was wrapped by electrostatic conjugation. Physical characterization of the complexes indicated that the gene complexes were successfully prepared. In vitro, cellular experiments showed excellent biocompatibility of PEI-g-PEG, efficient cellular uptake of the gene complexes, and successful expression of the corresponding fragments. Through gene silencing technique, PEI-g-PEG/PDGFR-α shRNA successfully inhibited the process of EMT in vitro. Furthermore, in vivo animal experiments suggested that this method could effectively inhibit the progression of fibroproliferative membranes of PVR. Herein, a feasible and promising clinical idea was provided for developing non-viral gene vectors and preventing fibroblastic eye diseases by RNA interference (RNAi) technology.
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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.
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Opacificação da Cápsula , Lentes Intraoculares , Nanopartículas Metálicas , Estruturas Metalorgânicas , Humanos , Ouro , Opacificação da Cápsula/etiologia , Opacificação da Cápsula/patologia , Opacificação da Cápsula/prevenção & controle , Lentes Intraoculares/efeitos adversosRESUMO
BACKGROUND: Herpes simplex keratitis (HSK) is the most common but serious infectious keratitis with high recurrence. It is predominantly caused by herpes simplex virus type 1 (HSV-1). The spread mechanism of HSV-1 in HSK is not entirely clear. Multiple publications indicate that exosomes participate in the intercellular communication process during viral infections. However, there is rare evidence that HSV-1 spreads in HSK by exosomal pathway. This study aims to investigate the relationship between the spread of HSV-1 and tear exosomes in recurrent HSK. METHODS: Tear fluids collected from total 59 participants were included in this study. Tear exosomes were isolated by ultracentrifugation, then identified by silver staining and western blot. The size was determined by dynamic light scattering (DLS). The viral biomarkers were identified by western blot. The cellular uptake of exosomes was studied using labelled exosomes. RESULTS: Tear exosomes were indeed enriched in tear fluids. Collected exosomes own normal diameters consistent with related reports. The exosomal biomarkers existed in tear exosomes. Labelled exosomes were successfully taken up by human corneal epithelial cells (HCEC) in large numbers in a short time. After cellular uptake, HSK biomarkers were detectable by western blot in infected cells. CONCLUSIONS: Tear exosomes should be the latent sites of HSV-1 in recurrent HSK and might be involved in the spread of HSV-1. Besides, this study verifies HSV-1 genes can be indeed transferred between cells by exosomal pathway, providing new inspiration for the clinical intervention and treatment as well as the drug discovery of recurrent HSK.
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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.