UNASSIGNED: Inflammation plays a significant role in the proliferation, migration, and differentiation of lens epithelial cells after cataract surgery, clinically manifested as posterior capsule opacification (PCO). This condition is typically treated with neodymium: yttrium-aluminum-garnet (Nd:YAG) laser capsulotomy. Our objective is to evaluate the association between blood-derived inflammatory markers and the development of clinically significant PCO necessitating treatment with laser capsulotomy.
UNASSIGNED: We conducted a retrospective review of charts for all patients who underwent Nd:YAG laser capsulotomy in our department between January 2021 and December 2022. The study included 70 patients who diagnosed with clinically significant PCO requiring treatment with Nd:YAG laser capsulotomy following cataract surgery, as well as 70 pseudophakic controls with no signs of PCO. Complete blood cell count parameters were obtained from medical records and the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) were calculated.
UNASSIGNED: The mean age of the Nd:YAG laser capsulotomy and control group was 71.83±8.46 and 72.27±9.98 years, respectively. The preoperative NLR scores for the Nd:YAG laser capsulotomy group (mean rank = 34.43) were statistically significantly higher than those of the control group (mean rank = 25.41) (p = 0.044). However, after adjusting for preoperative measurements, no statistically significant differences were observed between the groups for the other parameters.
UNASSIGNED: Preoperative NLR scores were higher in patients who developed clinically significant PCO requiring treatment with Nd:YAG laser capsulotomy. This finding suggests that patients with elevated systemic inflammation may be at an increased risk of developing PCO following cataract surgery. Further research is needed to evaluate the role of systemic inflammation in the pathogenesis of PCO.

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.

In his beautiful book, Consilience: The Unity of Knowledge, the eminent biologist Edward O Wilson, advocates the need for integration and reconciliation across the sciences. He defines consilience as \"literally a \'jumping together\' of knowledge with a linking of facts ... to create a common groundwork of explanation\". It is the premise of this paper that as much as basic biomedical research is in need of data generation using the latest available techniques- unifying available knowledge is just as critical. This involves the necessity to resolve contradictory findings, reduce silos, and acknowledge complexity. We take the cornea and the lens as case studies of our premise. Specifically, in this perspective, we discuss the conflicting and fragmented information on protein aggregation, oxidative damage, and fibrosis. These are fields of study that are integrally tied to anterior segment research. Our goal is to highlight the vital need for Wilson\'s consilience and unity of knowledge which in turn should lead to enhanced rigor and reproducibility, and most importantly, to greater understanding and not simply knowing.

UNASSIGNED: To assess the risk for uveitis, pseudophakic cystoid macular edema (PCME), and posterior capsular opacification (PCO) associated with the use of pupil expansion devices in cataract surgery.
UNASSIGNED: A retrospective comparative cohort study.
UNASSIGNED: Patients who underwent routine cataract surgery with and without pupil expansion devices at the Department of Ophthalmology, Bristol Eye Hospital, UK, between January 2008 and December 2017.
UNASSIGNED: This study included 39,460 eyes operated without a pupil expansion device and 699 eyes operated with the device. Odds ratios for uveitis and PCME when using a pupil expansion device were calculated using univariate and multivariate regression analysis, having age, gender, diabetes, pseudoexfoliation, and pupil expansion device as independent variables. Multivariate Cox regression controlling for age and gender was used to estimate hazard ratios (HR) for Nd : YAG laser capsulotomies.
UNASSIGNED: Postoperative uveitis and PCME were reported in 3.9% and 2.7% of the eyes operated with a pupil expansion device compared to 2.3% and 1.3% operated without the device (p=0.005 and p=0.002, respectively). In univariate regression analysis, eyes with pupil expansion devices showed a higher risk of postoperative uveitis or PMCE after cataract surgery (OR 1.88, 95%CI 1.39-2.55, p<0.001). In multivariate regression analysis, the risk for PMCE was greater among diabetic patients and in eyes with a pupil expansion device than in those without (OR 1.50, 95%CI 1.24-1.83, P<0.001; OR 1.90, 95%CI 1.16-3.11, P=0.01). In Cox regression analysis adjusted for the patient\'s age and gender, the use of a pupil expansion device was associated with higher Nd : YAG laser capsulotomy rates (HR 1.316, 95%CI 1.011-1.714, P=0.041).
UNASSIGNED: In our large cohort study, the use of pupil expansion devices in cataract surgery was associated with an increased risk of major postoperative complications. Effective anti-inflammatory treatment and follow-up are warranted in eyes operated with a pupil expansion device.

Purpose: The present study aimed to determine the dose-response relationship between targeted nanocarriers released from a novel, sustained release formulation and their ability to specifically deplete cells responsible for the development of posterior capsular opacification (PCO) in month-long, dynamic cell cultures. Methods: Injectable, thermosensitive poly(D,L-lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic-co-glycolic acid) triblock copolymer hydrogels were loaded with either a low or a high dose of doxorubicin-loaded antibody-targeted nanocarriers (G8:3DNA:Dox). Human rhabdomyosarcoma cells, selected for their expression of PCO marker brain-specific angiogenesis inhibitor 1 (BAI1), were kept under dynamic media flow and received either a low or high dose of nanocarriers. Cells were fixed and stained at predetermined time points to evaluate targeted depletion of BAI1+ cells. Results: A lower dose of nanocarriers in hydrogel depleted BAI1+ cells at a slower rate than the higher dose, whereas both reached over 90% BAI1+ cellular nonviability at 28 days. Both treatment groups also significantly lowered the relative abundance of BAI1+ cells in the population compared with the control group. Conclusions: Controlled release of a lower dose of nanocarriers can still achieve therapeutically relevant effects in the prevention of PCO, while avoiding potential secondary effects associated with the administration of a higher dose.

OBJECTIVE: To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells (LECs) under hyperosmotic stress.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.

BACKGROUND: Posterior capsular opacification (PCO) is the main reason affecting the long-term postoperative result of cataract patient, and it is well accepted that fibrotic PCO is driven by transforming growth factor beta (TGFβ) signaling. Ferroptosis, closely related to various ocular diseases, but has not been explored in PCO.
METHODS: RNA sequencing (RNA-seq) was performed on both TGF-β2 treated and untreated primary lens epithelial cells (pLECs). Differentially expressed genes (DEGs) associated with ferroptosis were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to investigate their biological function. Additionally, protein-to-protein interactions among selected ferroptosis-related genes by PPI network and the top 10 genes with the highest score (MCC algorithm) were selected as the hub genes. The top 20 genes with significant fold change values were validated using quantitative real-time polymerase chain reaction (qRT-PCR).
RESULTS: Our analysis revealed 1253 DEGs between TGF-β2 treated and untreated pLECs, uncovering 38 ferroptosis-related genes between two groups. Among these 38 ferroptosis-related genes,the most prominent GO enrichment analysis process involved in the response to oxidative stress (BPs), apical part of cell (CCs),antioxidant activity (MFs). KEGG were mainly concentrated in fluid shear stress and atherosclerosis, IL-17 and TNF signaling pathways, and validation of top 20 genes with significant fold change value were consistent with RNA-seq.
CONCLUSIONS: Our RNA-Seq data identified 38 ferroptosis-related genes in TGF-β2 treated and untreated pLECs, which is the first observation of ferroptosis related genes in primary human lens epithelial cells under TGF-β2 stimulation.

Background: Negative dysphotopsias (ND) are visual aberrations associated with in-the-bag optic intraocular lens (IOL) placement, causing arc-shaped or linear shadows. Reverse optic capture (ROC) is employed to prevent ND, yet it poses the risk of posterior capsular opacification (PCO) which usually develops within 2-5 years post-surgery due to the lens epithelial cells (LECs) proliferation and migration onto the posterior capsule. This can lead to a cloudy or hazy appearance in the visual field. Early identification of posterior capsular opacities is crucial to ensure timely intervention and minimize visual impairment. Cases Presentations: Two cases of acute and rapidly progressive PCO following cataract extraction (CE) and IOL placement using the ROC technique to prevent ND are reported at the Bascom Palmer Eye Institute. At the two-week postoperative follow-up, both patients reported a significant progressive decrease in vision in the treated eye, and severe posterior capsular opacities were observed. A diagnosis of PCO was confirmed, and successful visual rehabilitation was achieved through the performance of ND:YAG laser capsulotomy without complications. This case series represents the first reported instances of patients developing PCO within two weeks of CE and IOL placement using the ROC technique. Conclusions: This case series sheds light on the occurrence of posterior capsular opacities shortly after CE and IOL placement using the ROC technique. It highlights the importance of preoperative patient education, postoperative monitoring, and prompt management of potential complications in cataract surgery.

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.

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.