Zwitterionic modified and freeze-thaw reinforced foldable hydrogel as intraocular lens for posterior capsule opacification prevention.

Posterior capsule opacification (PCO) is a predominant postoperative complication, often leading to visual impairment due to the aberrant proliferation and adhesion of lens epithelial cells (LECs) and protein precipitates subsequent to intraocular lens (IOL) implantation. To address this clinical issue, a foldable and antifouling sharp-edged IOL implant based on naturally-derived cellulose hydrogel is synthesized. The mechanical strength and transparency of the hydrogel is enhanced via repeated freeze-thaw (FT) cycles. The incorporated zwitterionic modifications can remarkably prevent the incidence of PCO by exhibiting proteins repulsion and cell anti-adhesion properties. The graft of dopamine onto both the haptic and the periphery of the posterior surface ensures the adhesion of the hydrogel to the posterior capsule and impedes the migration of LECs without compromising transparency. In in vivo study, the zwitterionic modified foldable hydrogel exhibits uveal and capsular biocompatibility synchronously with no signs of inflammatory response and prevent PCO formation, better than that of commercialized and PEG-modified IOL. With foldability, endurability, antifouling effect, and adhesive to posterior capsule, the reported hydrogel featuring heterogeneous surface design displays great potential to eradicate PCO and attain post-operative efficacy after cataract surgery.

Transcriptome exploration of ferroptosis-related genes in TGFß- induced lens epithelial to mesenchymal transition during posterior capsular opacification development.

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 (TGFß) 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-ß2 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-ß2 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-ß2 treated and untreated pLECs, which is the first observation of ferroptosis related genes in primary human lens epithelial cells under TGF-ß2 stimulation.

Angle-closure glaucoma associated with vitreous prolapse after neodymium-doped yttrium-aluminumgarnet laser posterior capsulotomy.

Capsulotomy with neodymium-doped yttriumaluminum-garnet (Nd:YAG) laser is an effective treatment for posterior capsule opacification following cataract surgery. A wide opening of the posterior capsule associated with the ruptured anterior hyaloid can cause anterior chamber vitreous prolapse. Two patients who developed angle-closure glaucoma associated with vitreous prolapse following Nd:YAG laser posterior capsulotomy were successfully treated with antiglaucoma medication and peripheral iridotomies. Patient identification for potential risk factors and a careful postoperative follow-up are essential to avoid these serious complications.

Long-term real-life outcomes of the Clareon® hydrophobic intraocular lens: the Clarte study in 191 eyes : 3-years real-life outcomes of the Clareon® intraocular lens.

BACKGROUND: To describe and analyze the real-life refractive, functional and safety outcomes of the Clareon® intraocular lens (IOL) after 3 years. METHODS: Data was collected retrospectively for observational purposes between July 2017 and December 2019 in the ophthalmology department of Desgenettes military hospital in Lyon, France. Eyes that underwent cataract surgery with Claeron® implantation were consecutively included. Patients with a systemic or ocular condition that could affect the visual outcome were excluded. Postoperative corrected (CDVA) and uncorrected (UDVA) distance visual acuities as well as capsule and IOL transparency were assessed at 1 month and 3 years. RESULTS: A total of 326 eyes were analyzed at one month and 191 eyes were reassessed at the 3-year follow-up visit. At 3 years, the mean CDVA was 0.003 LogMAR (95% confidence interval [CI]: -0.003 to -0.01) and the mean UDVA was 0.075 (95% CI: 0.054 to 0.095). Three quarters of the patients had an UDVA ≥ 0.097 logMAR (20/25 Snellen equivalent) and 50% had an UDVA ≥ 0 (20/20). The absence of glistening was reported in 95.3% of cases and 4.7% [9] of patients experienced a clinically significant posterior capsular opacification (PCO) for which Nd:YAG treatment was required. CONCLUSIONS: This real-life study reports high-performance and stable long-term refractive outcomes of the Clareon® IOL with good safety in terms of PCO and glistening.

High incidence of sebaceous gland inflammation in aldose reductase-deficient mice.

Aldose reductase is a member of the 1B1 subfamily of aldo-keto reductase gene superfamily. The action of aldose reductase (AR) has been implicated in the pathogenesis of a variety of disease states, most notably complications of diabetes mellitus including neuropathy, retinopathy, nephropathy, and cataracts. To explore for mechanistic roles for AR in disease pathogenesis, we established mutant strains produced using Crispr-Cas9 to inactivate the AKR1B3 gene in C57BL6 mice. Phenotyping AR-knock out (ARKO) strains confirmed previous reports of reduced accumulation of tissue sorbitol levels. Lens epithelial cells in ARKO mice showed markedly reduced epithelial-to-mesenchymal transition following lens extraction in a surgical model of cataract and posterior capsule opacification. A previously unreported phenotype of preputial sebaceous gland swelling was observed frequently in male ARKO mice homozygous for the mutant AKR1B3 allele. This condition, which was shown to be accompanied by infiltration of proinflammatory CD3+ lymphocytes, was not observed in WT mice or mice heterozygous for the mutant allele. Despite this condition, reproductive fitness of the ARKO strain was indistinguishable from WT mice housed under identical conditions. These studies establish the utility of a new strain of AKR1B3-null mice created to support mechanistic studies of cataract and diabetic eye disease.

Transcriptome alterations in sf3b4-depleted zebrafish: Insights into cataract formation in retinitis pigmentosa model.

Posterior subcapsular cataract (PSC) frequently develops as a complication in patients with retinitis pigmentosa (RP). Despite numerous scientific investigations, the intricate pathomechanisms underlying cataract formation in individuals affected by RP remain elusive. Therefore, our study aims to elucidate the potential pathogenesis of cataracts in an RP model using splicing factor subunit 3b (sf3b4) mutant zebrafish. By analyzing our previously published transcriptome dataset, we identified that, in addition to RP, cataract was listed as the second condition in our transcriptomic analysis. Furthermore, we confirmed the presence of nucleus retention in the lens fiber cells, along with abnormal cytoskeleton expression in both the lens fiber cells and lens epithelial cells in sf3b4-depleted fish. Upon closer examination, we identified 20 differentially expressed genes (DEGs) that played a role in cataract formation, with 95 % of them related to the downregulation of structural lens proteins. Additionally, we also identified that among all the DEGs, 13 % were associated with fibrotic processes. It seems that the significant upregulation of inflammatory mediators, in conjunction with TGF-ß signaling, plays a central role in the cellular biology of PSC and posterior capsular opacification (PCO) in sf3b4 mutant fish. In summary, our study provides valuable insights into cataract formation in the RP model of sf3b4 mutants, highlighting its complexity driven by changes in structural lens proteins and increased cytokines/growth factors.

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

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

ZEPTO-assisted pseudophakic capsulotomy: Precision pulse technology for management of capsular contraction syndrome.

We describe a novel technique that uses precision pulse capsulotomy (PPC) to perform a secondary capsulotomy for the management of anterior capsule contraction syndrome (ACCS), a condition that comprises a late complication after cataract surgery and intraocular lens (IOL) implantation. Micropulse secondary capsulotomy offers a controlled and safe approach for patients with severe anterior capsule contraction syndrome and may be considered as an alternative surgical technique.

Impact of anterior capsule polishing on capsule opacification and capsule bend after age-related cataract surgery.

PURPOSE: To investigate the effect of anterior capsule polishing on postoperative capsule opacification and capsular bend in patients with age-related cataract displaying normal axial length. SETTING: Eye Hospital of Wenzhou Medical University at Hangzhou. DESIGN: Prospective self-controlled trial. METHODS: Patients with age-related cataracts aged 56 to 84 years displaying normal axial length were enrolled. Before surgery, a coin-toss method was used to randomly select 1 eye for intraoperative 360 degrees anterior capsule polishing (polishing group); the contralateral eye received no treatment (control group). Capsular bend index (CBI), anterior capsule opacification (ACO), posterior capsule opacification (PCO), and anterior capsule opening area (ACOA) were recorded at 1 week, 1 month, 3 months, 6 months, and 12 months postoperatively using swept-source optical coherence tomography and slitlamp examination. RESULTS: 21 patients (42 eyes) were enrolled. Within-group comparisons showed that both groups had significant differences in CBI between 1 week and 1 month postoperatively, and between 6 months and 12 months postoperatively ( P < .05). Between-group comparisons revealed a significant difference in CBI at 1 week postoperatively ( P < .05); at 12 months postoperatively, there was a significant difference in ACOA ( P < .05). There were no significant between-group differences regarding ACO or PCO at any timepoint ( P > .05). CONCLUSIONS: For patients with age-related cataracts and normal axial length, 360 degrees anterior capsule polishing can delay early capsular bag deformation without increasing the risks of ACO and PCO. This approach can also limit contraction of the anterior capsule opening.

Polydopamine based photothermal/photodynamic synchronous coating modified intraocular lens for efficient and safer posterior capsule opacification prevention.

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.

Knockout of TGF-ß receptor II by CRISPR/Cas9 delays mesenchymal transition of Lens epithelium and posterior capsule opacification.

Posterior capsule opacification (PCO) is the most common postoperative complication of cataract surgery. Transforming growth factor-ß (TGF-ß) is related to epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) that is proven to induce PCO formation in clinical and experimental studies. In this study, CRISPR sequences targeting exon of TGF-ßRII were knocked out with lentiviral transfection in LECs. Rabbits' PCO model was established and recombinant adeno-associated virus (AAV) for transferring the gRNA of TGF ßRII were intravitreally injected. SgRNA inhibited TGF-ßRII expression and human LECs proliferation. In TGF-ßRII knockout group, LECs motility and migration were suppressed, N-cadherin and vimentin expressions were significantly decreased, whereas E-cadherin was increased. The animal model showed that TGF-ßRII knockout in vivo was effective in suppressing PCO. The current study suggested that the CRISPR/Cas9 endonuclease system could suppress TGF-ßRII secretion, which participates in the EMT procedure of LECs in vitro and PCO in vivo. These findings might provide a new gene-editing approach and insight into a novel therapeutic strategy for PCO.

Improvements to a GLCM-based machine-learning approach for quantifying posterior capsule opacification.

BACKGROUND: Posterior capsular opacification (PCO) is a common complication following cataract surgery that leads to visual disturbances and decreased quality of vision. The aim of our study was to employ a machine-learning methodology to characterize and validate enhancements applied to the grey-level co-occurrence matrix (GLCM) while assessing its validity in comparison to clinical evaluations for evaluating PCO. METHODS: One hundred patients diagnosed with age-related cataracts who were scheduled for phacoemulsification surgery were included in the study. Following mydriasis, anterior segment photographs were captured using a high-resolution photographic system. The GLCM was utilized as the feature extractor, and a supported vector machine as the regressor. Three variations, namely, GLCM, GLCM+C (+axial information), and GLCM+V (+regional voting), were analyzed. The reference value for regression was determined by averaging clinical scores obtained through subjective analysis. The relationships between the predicted PCO outcome scores and the ground truth were assessed using Pearson correlation analysis and a Bland-Altman plot, while agreement between them was assessed through the Bland-Altman plot. RESULTS: Relative to the ground truth, the GLCM, GLCM+C, and GLCM+V methods exhibited correlation coefficients of 0.706, 0.768, and 0.829, respectively. The relationship between the PCO score predicted by the GLCM+V method and the ground truth was statistically significant (p < 0.001). Furthermore, the GLCM+V method demonstrated competitive performance comparable to that of two experienced clinicians (r = 0.825, 0.843) and superior to that of two junior clinicians (r = 0.786, 0.756). Notably, a high level of agreement was observed between predictions and the ground truth, without significant evidence of proportional bias (p > 0.05). CONCLUSIONS: Overall, our findings suggest that a machine-learning approach incorporating the GLCM, specifically the GLCM+V method, holds promise as an objective and reliable tool for assessing PCO progression. Further studies in larger patient cohorts are warranted to validate these findings and explore their potential clinical applications.

Hyperproliferation of Elschnig pearl-type posterior capsule opacification and spontaneous regression in two pseudophakic canine eyes.

OBJECTIVE: To describe the hyperproliferation of Elschnig pearl-type posterior capsule opacification and concurrent uveitis in two canine eyes after phacoemulsification, followed by spontaneous resolution of the Elschnig pearls. ANIMAL STUDIED: A 10-year-old castrated male Spitz (Case 1) and a 4-year-old spayed female Bichon Frise (Case 2). PROCEDURE: Elschnig pearls proliferating beyond the anterior capsulotomy site were observed in the right eye 10 months after bilateral diabetic cataract surgery (Case 1) and 7 months after unilateral cataract surgery (Case 2). In both cases, hyperproliferation occurred where the anterior capsule did not overlap with the intraocular lens (IOL), and was accompanied by aqueous flare. In Case 1, the pearls extended from the anterior capsule and adhered to the iris, causing focal posterior synechia. No other possible causes of uveitis were apparent. RESULTS: Initially, uveitis severity improved after the administration of topical and systemic anti-inflammatory drugs. However, uveitis recurred when the dosage of anti-inflammatory treatment was reduced. The Elschnig pearls underwent morphological changes throughout the follow-up period. In both cases, the pearls beyond the anterior capsulotomy resolved spontaneously after 5 months. Only a few pearls remained between the IOL and posterior capsule, and no recurrence of pearl proliferation was observed at the last follow-up. CONCLUSIONS: To the best of our knowledge, this is the first report of spontaneous Elschnig pearl regression in dogs. Lens-induced uveitis (LIU) may have been caused by anterior chamber hyperproliferative pearls. LIU associated with hyperproliferative pearls may be managed with appropriate anti-inflammatory treatment and monitoring.

Let-7c-3p suppresses lens epithelial-mesenchymal transition by inhibiting cadherin-11 expression in fibrotic cataract.

Fibrotic cataract, including anterior subcapsular cataract (ASC) and posterior capsule opacification, always lead to visual impairment. Epithelial-mesenchymal transition (EMT) is a well-known event that causes phenotypic alterations in lens epithelial cells (LECs) during lens fibrosis. Accumulating studies have demonstrated that microRNAs are important regulators of EMT and fibrosis. However, the evidence explaining how microRNAs modulate the behavior and alter the cellular phenotypes of the lens epithelium in fibrotic cataract is insufficient. In this study, we found that hsa-let-7c-3p is downregulated in LECs in human ASC in vivo as well as in TGFß2-induced EMT in vitro, indicating that hsa-let-7c-3p may participate in modulating the profibrotic processes in the lens. We then demonstrated that overexpression of hsa-let-7c-3p markedly suppressed human LEC proliferation and migration and attenuated TGFß2-induced EMT and injury-induced ASC in a mouse model. In addition, hsa-let-7c-3p mediated lens fibrosis by directly targeting the CDH11 gene, which encodes cadherin-11 protein, an important mediator in the EMT signaling pathway. It decreased cadherin-11 protein expression at the posttranscriptional level but not at the transcriptional level by binding to a specific site in the 3-untranslated region (3'-UTR) of CDH11 mRNA. Moreover, blockade of cadherin-11 expression with a specific short hairpin RNA reversed TGFß2-induced EMT in LECs in vitro. Collectively, these data demonstrated that hsa-let-7c-3p plays a clear role in attenuating ASC development and may be a novel candidate therapeutic for halting fibrosis and maintaining vision.

Visual outcomes and risk factors of uveitis cataract eyes after phacoemulsification and manual small-incision cataract surgery.

PURPOSE: To examine the visual outcomes and risk factors of uveitis cataract eyes after phacoemulsification and manual small-incision cataract surgery (MSICS). SETTING: Tertiary-care eye hospital in southern India. DESIGN: Retrospective interventional case series. METHODS: Of the uveitis eyes operated for cataract surgery between 2017 and 2020, eyes with a minimum of 6 months postoperative follow-up were included. Eyes with ocular trauma, lens subluxation, lens-induced uveitis, or retinal detachment-induced uveitis were excluded. Demography, visual acuity, intraoperative and postoperative records, and surgical outcomes were analyzed. RESULTS: 191 eyes of 191 patients with a mean age of 51.7 ± 14.4 years were included. Phacoemulsification was performed in 134 eyes, and 57 eyes underwent MSICS. Synechiolysis and pupil-expanding maneuvers were required in 74 eyes (38.7%). No differences were noted in the rates of complications between phacoemulsification and MSICS eyes, except at 1 year, where higher rates of posterior capsular opacification and vitritis were noted in MSICS eyes ( P = .018). The visual outcomes of eyes that underwent MSICS and phacoemulsification were comparable ( P = .463). In 12 eyes (13.5%), improvement in vision was not significant. CONCLUSIONS: This study shows phacoemulsification may be a preferred technique in uveitis cataracts, given the lesser incidence of postoperative complications. Patients should be counseled for realistic expectations.

Intraocular pressure increase after Nd:YAG laser capsulotomy and anterior segment optical coherence tomography analysis.

This study is to determine whether post-procedure intraocular pressure (IOP) increase is associated with the anterior chamber angle in cases of Neodymium: yttrium-aluminum garnet (Nd: YAG) laser capsulotomy. The study included 51 eyes with posterior capsule opacification. Initial IOP values of the patients were compared with IOP values without intraocular pressure-lowering administration at the end of the 1st hour, 1st day, 3rd day, and 7th day after Nd:YAG laser capsulotomy. The anterior segment angle configuration was evaluated using anterior segment optical coherence tomography analysis without dilatation before the procedure. The anterior chamber angle (ACA) and angle opening distances of 500 and 750 µm (AOD500 and AOD750) in the nasal and temporal quadrants were examined. The mean pre-laser IOP value only increased significantly at 1st hour post-laser (13.02 ± 3.02 mmHg vs 14.16 ± 4.07 mmHg, p = 0.016). In eyes with ACA below 40° in both the nasal and temporal quadrants, mean IOP increased significantly at 1st hour post-laser (p = 0.025 and p = 0.032, respectively), while it was not significant in eyes with ACA above 40° (p > 0.05). No correlation was found between ACA, AOD500, and AOD750 values and IOP changes at the first hour (p > 0.05). Except for the first hour after Nd:YAG laser capsulotomy, no significant increase in IOP was observed. This elevation was higher in eyes with ACA less than 40°. In patients with a narrow ACA, first-hour follow-up may be beneficial in terms of susceptibility to increased IOP.

Comparison of the Incidence of Nd:YAG Laser Capsulotomy Based on the Type of Intraocular Lens.

Background and Objectives: Posterior capsular opacification (PCO) is the most common long-term complication of successful cataract surgery and can cause visual impairment. We aimed to investigate the effects of intraocular lens (IOL) characteristics on PCO by comparing the incidence of neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy for different types of intraocular lenses. Materials and Methods: A retrospective analysis was performed on 2866 eyes that underwent cataract surgery between January 2010 and December 2017, with at least 5 years of follow-up. The IOLs used for surgery were the hydrophobic lenses SN60WF (Alcon, Fort Worth, TX, USA), ZCB00 (Johnson & Johnson Vision, Santa Ana, CA, USA), and MX60 (Bausch & Lomb, Rochester, NY, USA), and the hydrophilic lens MI60 (Bausch & Lomb, Rochester, NY, USA). We analyzed the incidence of Nd:YAG laser capsulotomy according to the type of IOL used. Results: The incidence of Nd:YAG laser capsulotomy was significantly higher with MI60 lenses (31.70%, 175/552 eyes) compared to SN60WF (7.90%, 113/1431 eyes), ZCB00 (10.06%, 64/636 eyes), and MX60 (10.57%, 13/123 eyes; p < 0.001) lenses. The incidence of Nd:YAG laser capsulotomy was significantly lower with the hydrophobic IOLs (8.68%, 190/2190 eyes) than with the hydrophilic IOL (31.70%, 175/552 eyes; p < 0.001). Over time, the rate of increase in the cumulative number of Nd:YAG laser capsulotomy cases was the highest with MI60. The cumulative rate of Nd:YAG laser capsulotomy during the first 3 years was 4.90% with SN60WF (70/1431 eyes), 6.76% with ZCB00 (43/636 eyes), 8.94% with MX60 (11/123 eyes), and 26.10% with MI60 (144/552 eyes) lenses. Conclusions: The incidence of PCO is influenced by the material of the IOLs. The hydrophilic IOL was associated with a higher rate of Nd:YAG laser capsulotomy than the hydrophobic IOLs, with a shorter time to Nd:YAG laser capsulotomy.

Understanding the Role of Yes-Associated Protein (YAP) Signaling in the Transformation of Lens Epithelial Cells (EMT) and Fibrosis.

Fibrotic cataracts, posterior capsular opacification (PCO), and anterior subcapsular cataracts (ASC) are mainly attributed to the transforming growth factor-ß (TGFß)-induced epithelial-to-mesenchymal transition (EMT) of lens epithelial cells (LECs). Previous investigations from our laboratory have shown the novel role of non-canonical TGFß signaling in the progression of EMT in LECs. In this study, we have identified YAP as a critical signaling molecule involved in lens fibrosis. The observed increase in nuclear YAP in capsules of human ASC patients points toward the involvement of YAP in lens fibrosis. In addition, the immunohistochemical (IHC) analyses on ocular sections from mice that overexpress TGFß in the lens (TGFßtg) showed a co-expression of YAP and α-SMA in the fibrotic plaques when compared to wild-type littermate lenses, which do not. The incubation of rat lens explants with verteporfin, a YAP inhibitor, prevented a TGFß-induced fiber-like phenotype, α-SMA, and fibronectin expression, as well as delocalization of E-cadherin and ß-catenin. Finally, LECs co-incubated with TGFß and YAP inhibitor did not exhibit an induction in matrix metalloproteinase 2 compared to those LECs treated with TGFß alone. In conclusion, these data demonstrate that YAP is required for TGFß-mediated lens EMT and fibrosis.

Six-Year Change in Cataract Surgical Coverage and Postoperative Visual Outcomes in Rural Southern China: The Yangxi Eye Study.

PURPOSE: The purpose of this study was to investigate a 6-year change in cataract surgical coverage (CSC), effective cataract surgical coverage (eCSC), and visual outcomes in an elderly population in rural southern China. DESIGN: This is a prospective population-based study with a 6-year follow-up. METHODS: The study included rural residents aged 50 years and above in southern China with comprehensive eye examinations at baseline and follow-up in 2014 and 2020, respectively. RESULTS: Five thousand six hundred thirty-eight participants underwent baseline examinations (mean age 66.1±10.2 y, 50.8% women); and 3141 (64.9%) of 4841 eligible survivors attended the 6-year follow-up. Cataract surgical coverage was 41.7% and 40.6% at baseline and follow-up, respectively, while eCSC were 32.6% and 26.6%. In multivariate models, the 6-year likelihood of cataract surgery decreased with older age [odds ratio (OR)=0.97 per year, 95% confidence interval (CI): 0.94, 0.99, P =0.012] and worse baseline presenting uncorrected visual acuity (PVA) in the worse-seeing eye (OR=0.35 per unit logarithm of the minimum angle of resolution (logMAR), 95% CI: 0.25, 0.48, P <0.001), and increased with prior cataract surgical history at baseline (OR=3.88, 95% CI: 1.91, 7.09, P <0.001). The likelihood of receiving effective cataract surgery decreased with worse baseline PVA in the worse eye (OR=0.49 per unit logMAR, 95% CI: 0.24, 0.97, P =0.042) and better-seeing eye (OR=0.68 per unit logMAR, 95% CI: 0.48, 0.95, P =0.026). Posterior capsular opacification was the main reason for PVA <6/18, reporting it in logMAR (0.5) in operated eyes (38.4% at baseline; 28.1% at follow-up). CONCLUSIONS: World Health Organization has established a global target of increasing eCSC by 30% before 2030, but no increase was found in rural southern China between 2014 and 2020, let alone reaching the World Health Organization target of 56.3%. Strategies to improve surgery incidence should focus on older persons and those with worse preoperative PVA.

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.