A novel single-base deletional mutation of MIP impairs protein distribution and cell-to-cell adhesion in autosomal dominant cataracts in a Chinese family.

Congenital cataracts are the leading cause of irreversible visual disability in children, and genetic factors play an important role in their development. In this study, targeted exome sequencing revealed a novel single-base deletional mutation of MIP (c.301delG; p.Ala101Profs*16) segregated with congenital punctate cataract in a Chinese family. The hydrophobic properties, and secondary and tertiary structures for truncated MIP were predicted to affect the function of protein by bioinformatics analysis. When MIP-WT and MIP-Ala101fs expression constructs were singly transfected into HeLa cells, it was found that the mRNA level showed no significant difference, while the protein level of the mutant was remarkably reduced compared to that of the wild-type MIP. Immunofluorescence images showed that the MIP-WT was principally localized to the plasma membrane, whereas the MIP-Ala101fs protein was aberrantly trapped in the cytoplasm. Furthermore, the cell-to-cell adhesion capability and the cell-to-cell communication property were both significantly reduced for MIP-Ala101fs compared to the MIP-WT (all *p < 0.05). This is the first report of the c.301delG mutation in the MIP gene associated with autosomal dominant congenital cataracts. We propose that the cataract is caused by the decreased protein expression and reduced cell-to-cell adhesion by the mutant MIP. The impaired trafficking or instability of the mutant protein, as well as compromised intercellular communication is probably a concurrent result of the mutation. The results expand the genetic and phenotypic spectra of MIP and help to better understand the molecular basis of congenital cataracts.

Targeting TBK1 attenuates ocular inflammation in uveitis by antagonizing NF-κB signaling.

Uveitis with complex pathogenesis is a kind of eye emergency involving refractory and blinding inflammation. Dysregulation of TANK binding kinase 1 (TBK1), which plays an important role in innate immunity, often leads to inflammatory diseases in various organs. However, the role of TBK1 in uveitis remains elusive. In this study, we identified that the mRNA expression level of TBK1 and its phosphorylation level were significantly increased in peripheral blood mononuclear cells (PBMCs) of patients with uveitis. Consistent with this, the expression of Tbk1 was elevated in the ocular tissues of uveitis rats and primary peritoneal macrophages while its phosphorylation levels, which present activation forms, were upregulated as well, accompanied by an increase in the level of nuclear factor-κB (NF-κB) and proinflammatory cytokines. In addition, inhibition of TBK1 may effectively reduce the inflammatory response of uveitis rats by blocking NF-κB entry into the nucleus and impeding the initiation of NLRP3 inflammasome- and caspase-1-mediated pyroptosis pathways.

Efficacy of bandage contact lens for the management of dry eye disease after cataract surgery.

PURPOSE: We aimed to evaluate the efficacy of bandage contact lens (BCL) for the management of dry eye disease (DED) after cataract surgery. METHODS: A total of 120 patients (140 eyes) with age-related cataract and DED were enrolled in this study. Patients underwent standard micro-incision phacoemulsification surgeries and were divided into control or BCL groups. Slit-lamp biomicroscopic examination, Ocular Surface Disease Index, keratograph analysis and Schirmer I test were executed, and the levels of tear inflammatory molecules were detected. RESULTS: In the control group, the NIAvg-BUT and Schirmer I test scores were significantly decreased at 1 week post-operation compared with baseline levels (P = 0.035 and P = 0.009, respectively). In the BCL group, the NIF-BUT and Schemer I test scores were significantly improved at 1 month after operation compared with the control group (P = 0.012 and P < 0.001, respectively). Levels of IL-6, IL-8 and ICAM-1 were significantly increased in the control group at 1 month after the operation (P = 0.005, P = 0.038 and P = 0.022, respectively), while there was no difference in the BCL group. The increase in the IL-6 level in the control group was significantly higher compared with that in the BCL group (P = 0.047). In DED patients, there were significant correlations between ocular surface parameters and inflammatory molecules. CONCLUSIONS: Cataract surgery could lead to the development or worsening of DED. The application of BCLs after cataract surgery could stabilize the ocular surface and tear film, improve the corneal healing and reduce the inflammation. Collectively, our findings suggested that proper use of BCLs after cataract surgery played an effective role in the management of DED. TRIAL REGISTRATION: ClinicalTrials, NCT04100031. Registered 18 September 2019-retrospectively registered.

Multiple cytokine analyses of aqueous humor from the patients with retinitis pigmentosa.

PURPOSE: Cataracts are the most common eye complications of retinitis pigmentosa (RP). This study aimed to investigate the cytokine profiles of the aqueous humor of RP with cataracts. METHODS: The aqueous humor was collected from RP eyes with cataract (RP group, n = 20) and age-related cataract eyes (ARC group, n = 20) during cataract surgery. The levels of 37 mediators were measured with multiplex fluorescent bead-based immunoassay and compared across groups. The correlation among chemokines, growth factors, and cytokines was analyzed with Spearman's rank correlation coefficient. RESULTS: Twelve cytokines (IL-1α, IL-1ß, IL-4, IL-10, TNF-α, IFN-γ, EGF, GM-CSF, PDGF-AB/BB, TGF-α, BMP-9, and E-selection) were below the limit of detection, and the detection rate of IL-6 was significantly higher in RP group than in the ARC group (P < 0.01). Compared with those in the control group, the aqueous humor levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-(IL-)8, interferon gamma-induced protein (IP)-10, hepatocyte growth factor (HGF), platelet-derived growth factor AA (PDGF-AA), matrix metalloproteinase-2 (MMP-2), MMP3, MMP-7, MMP-8, plasminogen activator inhibitor-1 (PAI-1), and thrombospondin-2 (TSP-2) in the RP group increased significantly (P < 0.01). A lower level of BMP-4 in the aqueous humor was observed in the RP patients than in the controls (P < 0.05). CONCLUSIONS: Significantly increased levels of PDGF-AA, MMP2, MMP3, MMP-7, MMP-8, PAI-1, and TSP-2 and lower levels of BMP-4 were found in the aqueous humor of RP patients. This result indicates a disturbance of the extracellular matrix (ECM) and cytokines in RP patients and suggests a possible role of these cytokines in the pathogenesis of capsular contraction syndrome (CCS) in RP patients.

Analysis of tear inflammatory molecules and clinical correlations in evaporative dry eye disease caused by meibomian gland dysfunction.

PURPOSE: To compare the levels of inflammatory molecules in tear samples between patients with meibomian gland dysfunction (MGD)-related evaporative dry eye (EDE) and healthy subjects and to analyze the correlations between the levels of tear inflammatory molecules and ocular surface parameters. METHODS: A total of 30 MGD-related EDE patients (48 eyes) and ten healthy volunteers (15 eyes) were enrolled. Dry eye-related examinations and questionnaires were obtained from all participants. The levels of nine inflammatory molecules were determined through multiplex bead analysis. RESULTS: Inflammatory molecules including ICAM-1, IFN-γ, CXCL8/IL-8, IL-6, TNF-α and IL-12p70 were detected in 100% of the patients, while IL-1α, IL-1ß and IL-10 were detected in 56.25%, 13.60% and 45.83% of the patients, respectively. Moreover, ICAM-1, IL-8, IL-6, TNF-α, IL-12p70 and IFN-γ were detected in 86.67-100% of the healthy subjects, and the detection rates of IL-10, IL-1α and IL-1ß were below 50%. The levels of IL-8, IL-6, IFN-γ and ICAM-1 were significantly higher in the patient group compared with the control group. In addition, IL-8 and IL-6 were negatively correlated with Schirmer I test. Besides, IFN-γ was negatively correlated with tear film breakup time. Furthermore, ICAM-1 and IL-6 were positively correlated with meibography score. CONCLUSIONS: Collectively, patients with MGD-related EDE had higher levels of inflammatory molecules in their tears, and some molecules were correlated with ocular surface parameters. These findings suggested that inflammation played an important role in MGD-related EDE, and several inflammatory molecules could be used in the diagnosis and the treatment of MGD-related EDE.

Regulation of angiogenin expression and epithelial-mesenchymal transition by HIF-1α signaling in hypoxic retinal pigment epithelial cells.

Choroidal neovascularization (CNV) is a major cause of vision loss in many retinal diseases. Hypoxia is determined to be a key inducer of CNV and hypoxia-inducible factor-1 (HIF-1) is an important transcription factor. Epithelial-mesenchymal transition (EMT) and the synthesis of proangiogenic cytokines make great contributions to the development of CNV. In the present study, the role of HIF-1α signaling in the regulation of angiogenin (ANG) expression and EMT in hypoxic retinal pigment epithelial cells was investigated. A significant elevation expression of ANG expression level in a mouse model of laser-induced CNV was demonstrated. In a hypoxic model of ARPE-19, an increased expression level of ANG and induction of EMT accompanied with stabilization and nucleus translocation of HIF-1α. Blockage of HIF-1α signaling resulted in inhibition of high expression of ANG and EMT features. The direct interaction between HIF-1α and ANG promoter region was identified by ChIP-qPCR. The association of RNase 4 mRNA level with HIF-1α signaling was also clarified in APRE-19. Moreover, the exogenous ANG translocated into the nucleus, enhanced 45S rRNA transcription, promoted cell proliferation and tube formation in human retinal microvascular endothelial cells. In conclusion, the hypoxic conditions regulate the expression of ANG and EMT via an activation of HIF-1α signaling. It provides molecular evidence for potential therapy strategies of treating CNV.

Identification of a novel lipofuscin pigment (iisoA2E) in retina and its effects in the retinal pigment epithelial cells.

Lipofuscin accumulation in retinal pigment epithelial (RPE) cells of the eye implicates the etiologies of Stargardt disease and age-related macular degeneration, a leading cause of blindness in the elderly. Here, we have identified a previously unknown RPE lipofuscin component. By one- and two-dimensional NMR techniques and mass spectrometry, we confirmed that this compound is a new type of pyridinium bisretinoid presenting an unusual structure, in which two polyenic side chains are attached to adjacent carbons of a pyridinium ring. This pigment is a light-induced isomer of isoA2E, rather than A2E, referred to as iisoA2E. This pigment is a fluorescent lipofuscin compound with absorbance maxima at ∼430 and 352 nm detected in human, pig, mouse, and bovine eyes. Formation of iisoA2E was found in reaction mixtures of all-trans-retinal and ethanolamine. Excess intracellular accumulation of this adduct in RPE cells in vitro leads to a significant loss of cell viability and caused membrane damage. Phospholipase D-mediated phosphodiester cleavage of the A2PE series generated isoA2E and iisoA2E, in addition to A2E, thus corroborating the presence of isoA2PE and iisoA2PE that may serve as biosynthetic precursors of isoA2E and iisoA2E.

Cataract-related variant R114C increases ßA3-crystallin susceptibility to environmental stresses by disrupting the protein senior structure.

Congenital cataract is a major cause of childhood blindness worldwide, with crystallin mutations accounting for over 40 % of gene-mutation-related cases. Our research focused on a novel R114C mutation in a Chinese family, resulting in bilateral coronary cataract with blue punctate opacity. Spectroscopic experiments revealed that ßA3-R114C significantly altered the senior structure, exhibiting aggregation, and reduced solubility at physiological temperature. The mutant also displayed decreased resistance and stability under environmental stresses such as UV irradiation, oxidative stress, and heat. Further, cellular models confirmed its heightened sensitivity to environmental stresses. These data suggest that the R114C mutation impairs the hydrogen bond network and structural stability of ßA3-crystallin, particularly at the boundary of the second Greek-key motif. This study revealed the pathological mechanism of ßA3-R114C and may help in the development of potential treatment strategies for related cataracts.

Truncation mutations of CRYGD gene in congenital cataracts cause protein aggregation by disrupting the structural stability of γD-crystallin.

Congenital cataracts, a prevalent cause of blindness in children, are associated with protein aggregation. γD-crystallin, essential for sustaining lens transparency, exists as a monomer and exhibits excellent structural stability. In our cohort, we identified a nonsense mutation (c.451_452insGACT, p.Y151X) in the CRYGD gene. To explore the effect of truncation mutations on the structure of γD-crystallin, we examined the Y151X and T160RfsX8 mutations, both located in the Greek key motif 4 at the cellular and protein level in this study. Both truncation mutations induced protein misfolding and resulted in the formation of insoluble aggregates when overexpressed in HLE B3 and HEK 293T cells. Moreover, heat, UV irradiation, and oxidative stress increased the proportion of aggregates of mutants in the cells. We next purified γD-crystallin to estimate its structural changes. Truncation mutations led to conformational disruption and a concomitant decrease in protein solubility. Molecular dynamics simulations further demonstrated that partial deletion of the conserved domain within the Greek key motif 4 markedly compromised the overall stability of the protein structure. Finally, co-expression of α-crystallins facilitated the proper folding of truncated mutants and mitigated protein aggregation. In summary, the structural integrity of the Greek key motif 4 in γD-crystallin is crucial for overall structural stability.

New insights into change of lens proteins' stability with ageing under physiological conditions.

BACKGROUND: Age-related cataract, which presents as a cloudy lens, is the primary cause of vision impairment worldwide and can cause more than 80% senile blindness. Previous studies mainly explored the profile of lens proteins at a low concentration because of technical limitations, which could not reflect physiological status. This study focuses on protein stability changes with ageing under physiological conditions using a novel equipment, Unchained Labs (Uncle), to evaluate protein thermal stability. METHODS: Samples were assessed through Unchained Labs, size-exclusion chromatography, western blot and biophysics approaches including the Thioflavin T, ultraviolet and internal fluorescence. RESULTS: With age, the melting temperature value shifted from 67.8°C in the young group to 64.2°C in the aged group. Meanwhile, crystallin may form more isomeric oligomers and easy to be degraded in aged lenses. The spectroscopic and size-exclusion chromatography results show a higher solubility after administrated with lanosterol under the environmental stress. CONCLUSION: We are the first to explore rabbit lens protein stability changes with ageing using biophysical methods under physiological conditions, and this study can conclude that the structural stability and solubility of lens proteins decrease with ageing. Additionally, lanosterol could aid in resolving protein aggregation, making it a potential therapeutic option for cataracts. So, this study provides cataract models for anti-cataract drug developments.

The 18th amino acid glycine plays an essential role in maintaining the structural stabilities of γS-crystallin linking with congenital cataract.

γS-crystallin is particularly rich in the embryonic nuclear region and is crucial to the maintenance of lens transparency and optical properties. Gene mutations in crystallin are the main factors leading to congenital hereditary cataracts, which are a major cause of visual impairment in children. Some mutations located in the 18th amino acid glycine of γS-crystallin were reported to be linking with congenital cataracts. However, the pathogenic mechanism has not been elucidated. Interestingly, we previously identified a novel variant of γS-crystallin (c.53G > A; p. G18D) with progressive cortical and sutural congenital cataracts in one Chinese family. In this study, we purified the γS-crystallin wildtype and mutant proteins to investigate the effects of the G18D mutation on the structural stability of γS-crystallin. The results showed that there were tertiary structural differences between the wild-type γS-crystallin and the G18D variant. The mutation significantly impaired the stability of γS-crystallin under environmental stress and promoted aggregation. Furthermore, molecular dynamics (MD) simulations showed that the mutation altered H-bonding and surface electrostatic potential. Significantly decreased stability along with an increased tendency to aggregate under environmental stress may be the major pathogenic factors for cataracts induced by the G18D mutation.

Heteromeric formation with ßA3 protects the low thermal stability of ßB1-L116P.

BACKGROUND/AIMS: Congenital cataract is the leading cause of visual disability and blindness in childhood. ßB1-crystallin (CRYBB1) comprises about 1/10th of crystallin structural proteins, forming heteromers to maintain lens transparency. We previously reported a CRYBB1 mutation (c.347T>C, p.L116P) affecting 16 patients in a congenital nuclear cataract family. In this study, we investigate the underlying pathogenic mechanism of ßB1-L116P. METHODS: Protein isolation, size-exclusion chromatography, spectroscopy, Uncle stability screens and molecular dynamics simulations were used to assess ßA3- and ßB1-crystallin thermal stability, structural properties and heteromer formation. RESULTS: Cells that overexpressed ßB1-L116P tended to form aggregates and precipitations under heat-shock stress. Thermal denaturation and time-dependent turbidity experiments showed that thermal stability was significantly impaired. Moreover, protein instability appeared to increase with elevated concentrations detected by the Uncle system. Additionally, ßA3 had a relative protective effect on ßB1-L116P after heteromers were formed, although ßA3 was relatively unstable and was usually protected by basic ß-crystallins. Molecular dynamic simulations revealed that L116P mutation altered the hydrophobic residues at the surface around the mutant site, providing solvents more access to the internal and hydrophobic parts of the protein. CONCLUSIONS: Decreased ßB1-crystallin thermal stability in the presence of the cataract-related L116P mutation contributes significantly to congenital cataract formation. Moreover, its formation of heteromers with ßA3 protects against the low thermal stability of ßB1-L116P.

Cataract-causing mutations S78F and S78P of γD-crystallin decrease protein conformational stability and drive aggregation.

Congenital cataract is the leading cause of childhood blindness, which primarily results from genetic factors. γD-crystallin is the most abundant γ-crystallin and is essential for maintaining lens transparency and refractivity. Numerous mutations in γD-crystallin have been reported with unclear pathogenic mechanism. Two different cataract-causing mutations Ser78Phe and Ser78Pro in γD-crystallin were previously identified at the same conserved Ser78 residue. In this work, firstly, we purified the mutants and characterized for the structural change using fluorescence spectroscopy, circular dichroism (CD) spectroscopy, and size-exclusion chromatography (SEC). Both mutants were prone to form insoluble precipitates when expressed in Escherichia coli strain BL21 (DE3) cells. Compared with wild-type (WT), both mutations caused structural disruption, increased hydrophobic exposure, decreased solubility, and reduced thermal stability. Next, we investigated the aggregation of the mutants at the cellular level. Overexpression the mutants in HLE-B3 and HEK 293T cells could induce aggresome formations. The environmental stresses (including heat, ultraviolet irradiation and oxidative stress) promoted the formation of aggregates. Moreover, the intracellular S78F and S78P aggregates could be reversed by lanosterol. Molecular dynamic simulation indicated that both mutations disrupted the structural integrity of Greek-key motif 2. Hence, our results reveal the vital role of conserved Ser78 in maintaining the structural stability, which can offer new insights into the mechanism of cataract formation.

Prophylaxis of posterior capsule opacification through autophagy activation with indomethacin-eluting intraocular lens.

Posterior capsule opacification (PCO) is the most common long-term postoperative complication of cataract surgery, leading to secondary vision loss. Optimized intraocular lens (IOL) structure and appropriate pharmacological intervention, which provides physical barriers and biological inhibition, respectively, can block the migration, proliferation, and epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) for PCO prophylaxis. Herein, a novel indomethacin-eluting IOL (INDOM-IOL) with an optimized sharper edge and a sustained drug release behavior was developed for PCO prevention. Indomethacin (INDOM), an ophthalmic non-steroidal anti-inflammatory drug (NSAID) used for postoperative ocular inflammation, was demonstrated to not only be able to suppress cell migration and down-regulate the expression of cyclooxygenase-2 (COX-2) and EMT markers, including alpha-smooth muscle actin (α-SMA) and cyclin D1, but also promote the autophagy activation in LECs. Additionally, autophagy was also verified to be a potential therapeutic target for the down-regulation of EMT in LECs. The novel IOL, serving as a drug delivery platform, could carry an adjustable dose of hydrophobic indomethacin with sustained drug release ability for more than 28 days. In the rabbit PCO model, the indomethacin-eluting IOL showed excellent anti-inflammatory and anti-PCO effects. In summary, indomethacin is an effective pharmacological intervention in PCO prophylaxis, and the novel IOL we developed prevented PCO in vivo under its sustained indomethacin release property, which provided a promising approach for PCO prophylaxis in clinical application.

Insight into Pathogenic Mechanism Underlying the Hereditary Cataract Caused by ßB2-G149V Mutation.

Congenital cataracts account for approximately 5-20% of childhood blindness worldwide and 22-30% of childhood blindness in developing countries. Genetic disorders are the primary cause of congenital cataracts. In this work, we investigated the underlying molecular mechanism of G149V point missense mutation in ßB2-crystallin, which was first identified in a three-generation Chinese family with two affected members diagnosed with congenital cataracts. Spectroscopic experiments were performed to determine the structural differences between the wild type (WT) and the G149V mutant of ßB2-crystallin. The results showed that the G149V mutation significantly changed the secondary and tertiary structure of ßB2-crystallin. The polarity of the tryptophan microenvironment and the hydrophobicity of the mutant protein increased. The G149V mutation made the protein structure loose and the interaction between oligomers was reduced, which decreased the stability of the protein. Furthermore, we compared ßB2-crystallin WT and the G149V mutant with their biophysical properties under environmental stress. We found that the G149V mutation makes ßB2-crystallin more sensitive to environmental stresses (oxidative stress, UV irradiation, and heat shock) and more likely to aggregate and form precipitation. These features might be important to the pathogenesis of ßB2-crystallin G149V mutant related to congenital cataracts.

Lens regeneration in situ using hESCs-derived cells -similar to natural lens.

Lens itself has limited regeneration functionality, thus we aimed to create regenerated lens with biological function to treat cataracts rather than the intraocular lens used in cataract surgery. We induced exogenous human embryonic stem cells to directionally differentiate into lens fate like cells in vitro, mixed these cells with hyaluronate, and then implanted the mixture into lens capsule to regenerate in vivo. We successfully achieved near-complete lens regeneration, and the thickness of the regenerated lens reached 85% of the contralateral eye, showing the characteristics of biconvex shape, transparency, and a thickness and diopter close to that of natural lenses. Meanwhile, the participation of Wnt/PCP pathway in lens regeneration was verified. The regenerated lens in this study was the most transparent, thickest, and most similar to the original natural lens that has thus far been reported. Overall, these findings offer a new therapeutic strategy for cataracts and other lens diseases.

A novel gatifloxacin-loaded intraocular lens for prophylaxis of postoperative endophthalmitis.

Postoperative endophthalmitis (POE) has been the most threatening complication after cataract surgery, which perhaps can be solved by the antibiotic-loaded intraocular lens (IOL). However, most drug-loaded IOLs demonstrate insufficient drug quantity, short release time, increased implantation-related difficulties or other noticeable drawbacks. To prevent POE and to address these deficiencies, a drug-loaded copolymer IOL, prepared from poly (urethane acrylate) prepolymer, isobornyl methacrylate (IBOMA), N-vinyl-2-pyrrolidone (NVP), Irgacure 819, RUVA-93, and gatifloxacin (GAT), was rapidly fabricated via photocuring and by using a 3D-printed mold. This composite displayed an outstanding and controllable GAT release behavior in vitro, a high light transmittance, and a moderate refractive index. Also, it demonstrated improved strain stress and elongation compared with the reference commercial acrylic IOL material. In vivo tests demonstrated satisfying released drug concentration at the early treatment stage. In vitro and in vivo studies further confirmed the remarkable bacterial inhibition and prevention of POE by the proposed IOL, which also displayed good biocompatibility. These findings suggested that the GAT-loaded IOL could be a promising implant to prevent and cure POE, also the proposed methods could inspire more designs for various medical applications.

Comparison Study of Anterior Capsule Contraction of Hydrophilic and Hydrophobic Intraocular Lenses Under the Same Size Capsulotomy.

Purpose: To compare anterior capsule contraction of two kinds of hydrophilic and hydrophobic acrylic intraocular lenses (IOLs) under the same size capsulotomy with femtosecond laser-assisted cataract surgery (FLACS). Methods: A total of 320 eyes in 320 patients who underwent FLACS were included. The patients were scheduled to have hydrophilic acrylic IOLs (MI60, 509M) and hydrophobic acrylic IOLs (iSert250, ZCB00) implanted. Visual acuity and anterior segment photography using a slit lamp microscope were performed at postoperative one week, one month, three months, and one year. Results: The contraction of the anterior capsule opening area (mm2) and circumference (mm) in the hydrophilic group were larger than that of the hydrophobic group from postoperative one week to one year (P < 0.001, P < 0.001, respectively). The postoperative contraction of the capsule opening area in MI60 was larger than in 509M (P < 0.001) and larger in 509M than in iSert250 and ZCB00 (P = 0.008, P = 0.019, respectively), but no difference was observed between iSert250 and ZCB00 (P = 0.867). During postoperative one to three months, all groups had the maximum capsule contraction (P < 0.001). Conclusions: Under the same size capsulotomy with FLACS, the postoperative anterior capsule contraction induced by hydrophobic IOLs was less than that induced by hydrophilic IOLs. Among the four IOLs, the capsule contraction was largest in MI60, followed by 509M, and least in iSert250 and ZCB00, which was time-dependent. Translational Relevance: Our findings implied that patients with a high risk of ACC should choose hydrophobic IOLs, as well as nonsteroidal anti-inflammatory drugs may be used for a longer period in patients with high risk of capsule contraction syndrome.

Recent Advances of Intraocular Lens Materials and Surface Modification in Cataract Surgery.

Advances in cataract surgery have increased the demand for intraocular lens (IOL) materials. At present, the progress of IOL materials mainly contains further improving biocompatibility, providing better visual quality and adjustable ability, reducing surgical incision, as well as dealing with complications such as posterior capsular opacification (PCO) and ophthalmitis. The purpose of this review is to describe the research progress of relevant IOL materials classified according to different clinical purposes. The innovation of IOL materials is often based on the common IOL materials on the market, such as silicon and acrylate. Special properties and functions are obtained by adding extra polymers or surface modification. Most of these studies have not yet been commercialized, which requires a large number of clinical trials. But they provide valuable thoughts for the optimization of the IOL function.

Cell Wall Destruction and Internal Cascade Synergistic Antifungal Strategy for Fungal Keratitis.

Fungal keratitis is one of the most common blindness-causing diseases, but clinical antifungal treatment remains a challenge. The fungal cell wall and biofilm matrix which severely confine the drug preparation are the critical obstructive factors to therapeutic effects. Herein, we report ethylenediaminetetraacetic acid (EDTA) modified AgCu2O nanoparticles (AgCuE NPs) to disrupt the cell wall and then eradicate C. albicans through the internal cascade synergistic effects of ion-released chemotherapy, chemodynamic therapy, photodynamic therapy, and mild photothermal therapy. AgCuE NPs exhibited excellent antifungal activity both in preventing biofilm formation and in destroying mature biofilms. Furthermore, AgCuE NP based gel formulations were topically applied to kill fungi, reduce inflammation, and promote wound healing, using optical coherence tomography and photoacoustic imaging to monitor nanogel retention and therapeutic effects on the infected murine cornea model. The AgCuE NP gel showed good biosafety and no obvious ophthalmic and systemic side effects. This study suggests that the AgCuE NP gel is an effective and safe antifungal strategy for fungal keratitis with a favorable prognosis and potential for clinical translation.