A role for YAP/FOXM1/Nrf2 axis in oxidative stress and apoptosis of cataract induced by UVB irradiation.

This study aims to investigate the hypothesis that Yes-associated protein (YAP) significantly regulates antioxidant potential and anti-apoptosis in UVB-induced cataract by exploring the underlying molecular mechanisms. To investigate the association between YAP and cataract, various experimental techniques were employed, including cell viability assessment, Annexin V FITC/PI assay, measurement of ROS production, RT-PCR, Western blot assay, and Immunoprecipitation. UVB exposure on human lens epithelium cells (HLECs) reduced total and nuclear YAP protein expression, increased cleaved/pro-caspase 3 ratios, decreased cell viability, and elevated ROS levels compared to controls. Similar Western blot results were observed in in vivo experiments involving UVB-treated mice. YAP knockdown in vitro demonstrated a decrease in the protein expression of FOXM1, Nrf2, and HO-1, which correlated with the mRNA expression, accompanied by an increase in cell apoptosis, caspase 3 activation, and the release of ROS. Conversely, YAP overexpression mitigated these effects induced by UVB irradiation. Immunoprecipitation revealed a FOXM1-YAP interaction. Notably, inhibiting FOXM1 decreased Nrf2 and HO-1, activating caspase 3. Additionally, administering the ROS inhibitor N-acetyl-L-cysteine (NAC) effectively mitigated the apoptotic effects induced by oxidative stress from UVB irradiation, rescuing the protein expression levels of YAP, FOXM1, Nrf2, and HO-1. The initial findings of our study demonstrate the existence of a feedback loop involving YAP, FOXM1, Nrf2, and ROS that significantly influences the cell apoptosis in HLECs under UVB-induced oxidative stress.

Effect of Decentration, Rotation, and Tilt on Objective Optical Quality of Plate Haptic Toric Intraocular Lenses in the Early Postoperative Period.

Purpose: This study aimed to determine the influence of decentration, rotation, and tilt on objective optical quality of plate haptic toric intraocular lenses (tIOLs). Methods: The area ratio of modulation transfer function (MTF), strehl ratio of point spread function (PSF), and higher order aberrations (HOAs) for 3 mm and 5 mm pupil diameter (PD) were evaluated at postoperative 1 month. The retroillumination images pictured by OPD-scan III were used to quantify the degree of decentration and rotation, whereas the tIOL tilt was directly obtained by the tilt aberration. Patients were separated into two subgroups based on tIOL misalignment cutoff values. Results: There were 29 eyes (24 patients) in the study. The decentration of more than 0.25 mm did not substantially differ from those less than or equal to 0.25 mm. PSF of 3 mm PD and MTF, intraocular HOAs, and trefoil aberration for 3 mm and 5 mm PD significantly deteriorated with a rotation of more than 3 degrees, whereas only intraocular HOAs for 5 mm PD and coma for 3 mm and 5 mm PD were significantly severe with a tilt of more than 0.1 µm and 0.25 µm in corresponding PD. Furthermore, tIOL rotation and tilt were highly correlated with intraocular trefoil aberration and coma, respectively. Conclusions: The decentration of the monofocal bitoric IOLs is more tolerant to optical quality degradation after 1 month of surgery but more sensitive to intraocular trefoil aberration caused by rotation and coma aberration induced by tilt. Translational Relevance: As far as we know, this is the first study to investigate the relationship between the plate haptic bitoric IOL misalignment and objective optical quality measured by OPD-scan III in the real world, which may provide reference information for IOL selection to improve surgical outcomes.

A Bayesian network meta-analysis on comparisons of intraocular lens power calculation methods for paediatric cataract eyes.

The study aimed to compare and rank the accuracy of formulas for calculating intraocular lens (IOL) power in paediatric eyes in a systematic way. A literature search was conducted in Pubmed, Web of Science, Cochrane Library, and EMBASE by December 2021. Combined with traditional and network meta-analysis, we analysed the percentages of paediatric eyes with prediction error (PE) within ±0.50 dioptres (D) and ±1.00 D as the outcome measurements among different formulas. Subgroup analyses stratified by age were also undertaken. Thirteen studies with 1781 eyes comparing 8 calculation formulas were included. For the traditional meta-analysis results, Sanders-Retzlaff-Kraff theoretical (SRK/T) (risk ratios (RR), 1.15; 95% confidence intervals (CI), 1.03-1.30) performed significantly better than the SRKII formula for the percentage of eyes with PE within ±0.50 D. In addition, SRK/T (RR, 1.10; 95% CI, 1.02-1.18) and Holladay 1(RR, 1.15; 95% CI, 1.01-1.30) both performed significantly better than the SRKII formula for the percentage of eyes with PE within ±1.00 D. Considering the ranking based on the surface under the cumulative ranking curve (SUCRA) by Bayesian method, the top four formulas were Barrett Universal II (UII), Haigis, Holladay 1, and SRK/T on the percentage of PE within ±0.50 D, whereas the top four formulas were Barrett UII, Holladay 1, SRK/T, and Hoffer Q formulas on the percentage of PE within ±1.00D. Concerning both outcome measurements of rank probabilities, the top three Barrett UII, SRK/T, and Holladay 1 formulas were considered to provide more accuracy for IOL power calculation in paediatric cataract eyes, and Barrett UII tends to perform better in older children.

ceRNA network construction and identification of hub genes as novel therapeutic targets for age-related cataracts using bioinformatics.

Background: The aim of this study is to investigate the genetic and epigenetic mechanisms involved in the pathogenesis of age-related cataract (ARC). Methods: We obtained the transcriptome datafile of th ree ARC samples and three healthy, age-matched samples and used differential expression analyses to identify the differentially expressed genes (DEGs). The differential lncRNA-associated competing endogenous (ceRNA) network, and the protein-protein network (PPI) were constructed using Cytoscape and STRING. Cluster analyses were performed to identify the underlying molecular mechanisms of the hub genes affecting ARC progression. To verify the immune status of the ARC patients, immune-associated analyses were also conducted. Results: The PPI network identified the FOXO1 gene as the hub gene with the highest score, as calculated by the Maximal Clique Centrality (MCC) algorithm. The ceRNA network identified lncRNAs H19, XIST, TTTY14, and MEG3 and hub genes FOXO1, NOTCH3, CDK6, SPRY2, and CA2 as playing key roles in regulating the pathogenesis of ARC. Additionally, the identified hub genes showed no significant correlation with an immune response but were highly correlated with cell metabolism, including cysteine, methionine, and galactose. Discussion: The findings of this study may provide clues toward ARC pathogenic mechanisms and may be of significance for future therapeutic research.

The growth and shape of the eyeball and crystalline lens in utero documented by fetal MR imaging.

Purpose: To study the growth model, shape, and developmental relationship of lens and eyeball, we used two-dimensional Magnetic Resonance (MR) imaging to investigate gestationally age-related changes in the selected ocular parameters in vivo. Materials and methods: We retrospectively reviewed the MR images from 126 fetuses ranging from 21 to 39 weeks' gestation. Ocular parameters on MR imaging of transverse plane were measured including lens diameter (LD), anteroposterior lens diameter (APLD), lens surface area (LS), globe diameter (GD), anteroposterior globe diameter (APGD), globe surface area (GS). The growth model of each biometric against gestational age (GA), aspect ratio of lens and globe (LD/APLD and GD/APGD), and growing relationship between the ratio of lens and globe surface area (LS/GS) were studied by statistical analysis. Results: The growth model of most biometry for gestational age is logarithmic, except for the diameter of the ocular globe (GD and APGD) showing a quadratic growth pattern. Our study showed that the lens was consistently larger in the transverse than the anteroposterior diameters during 21-39 weeks(P < 0.001). Besides, the ratio of surface area (LS/GS) was not significantly changing with GA(P = 0.4908), while the increase of LS was significantly accorded with that of GS(P < 0.001). Conclusion: The lens shape throughout fetal life may take part in the process, shape changing from vertical ellipsoid, spherical to transversal ellipsoid, based on the logarithmically increased ratio of lens transverse and anteroposterior diameters. In the meanwhile, the aspect ratio of eyeball in late fetal life may imply a gradually spherical shape during gestation. Nomogram data from this study may provide appropriate information about morphological changes in the fetal lens and the synchronous relationship between lens and eyeball.

Prevalence and Risk Factors for Adult Cataract in the Jingan District of Shanghai.

Purpose: We report the prevalence of age-related cataract (ARC) in the Jingan district of Shanghai and analyze the risk factors for ARC to be better prepared for the increasing burden of cataracts as a significant cause of visual impairment worldwide. Methods: From March to June 2010, a population-based, cross-sectional study was conducted in a community selected by stratified cluster sampling in the Jingan district of Shanghai. Residents aged 40 and older were recruited and investigated by questionnaires and ophthalmic examination. Univariate and multivariate logistic regression models were used to evaluate the association of these risk factors with any cataract. Results: A total of 2894 subjects aged 40 years and above were included in our study. Nine hundred forty-eight people (32.8%) were diagnosed with cataract, including 845 with bilateral cataracts (29.2%) and 292 with moderate and severe visual impairment (low vision, 10.1%). There were significant differences in low vision among different age groups and gender (Χ2 age = 84.420, P age < 0.001, Χ2 gender = 7.696, P gender = 0.021). For any cataract, we found age (OR = 1.107, 95% CI: 1.094-1.120) and refractive error (OR = 1.352, 95% CI: 1.127-1.622) were independent risk factors. Conclusion: The prevalence of cataract is estimated to be nearly one-third of the sample, increasing with age. We provided further evidence that age and refractive error are independent cataract risk factors.

Presbyopia-Correcting Intraocular Lenses Implantation in Eyes After Corneal Refractive Laser Surgery: A Meta-Analysis and Systematic Review.

Purpose: To assess the efficacy, safety, and predictability of presbyopia-correcting intraocular lenses (IOLs) in cataract patients with previous corneal refractive surgery. Methods: A systematic literature search was performed to identify studies evaluating the clinical outcomes of presbyopia-correcting IOLs implantation in cataract surgery after laser refractive surgery. Outcomes were efficacy, safety and predictability parameters. Results: The authors identified 13 studies, involving a total of 128 patients and 445 eyes. Presbyopia-correcting IOLs were effective at improving distance, intermediate and near visual acuity aftercataract surgery. The proportion of post-laser surgery eyes with uncorrected distance visual acuity (UDVA) ≥ 20/25 was 0.82 [95% confidence interval (CI), 0.74-0.90] and the pooled rates of spectacle independence at near, intermediate, and far distances were 0.98 (95% CI, 0.94-1.00), 0.99 (95% CI, 0.95-1.00) and 0.78 (95% CI, 0.65-0.94) respectively. The percentage of participants who suffered from halos and glare was 0.40 (95% CI, 0.25-0.64) and 0.31 (95% CI, 0.16-0.60), respectively. The predictability had a percentage of 0.66 (95% CI, 0.57-0.75) and 0.90 (95% CI, 0.85-0.96) of eyes within ±0.5 diopters (D) and ±1.0 D from the targeted spherical equivalent. Conclusions: Presbyopia-correcting IOLs provide satisfactory results in terms of efficacy, safety and predictability in patients with previous corneal refractive surgery, but have a higher risk of photopic side effects such as halos and glare.

Titanium carbide MXenes coupled with cadmium sulfide nanosheets as two-dimensional/two-dimensional heterostructures for photocatalytic hydrogen production.

Two-dimensional (2D)/2D heterostructures with close contact are believed to be important for photocatalysis owing to a 2D ultrathin structure, a large surface area, and an efficient carrier separation or transfer. In this study, we designed and prepared a unique 2D/2D cadmium sulfide (CdS) nanosheet (NS)@titanium carbide (Ti3C2) MXene composite photocatalyst. The results show that the CdS NSs can be controllably assembled on conductive Ti3C2 MXene via a one-step hydrothermal strategy. The 2D/2D CdS NS@Ti3C2 MXene composites with 5 mg of Ti3C2 MXene show a higher photocatalytic performance (1.73 mmol h-1 g-1) than pure CdS NSs (0.37 mmol h-1 g-1) and CdS NS@Ti3C2 MXene composites with other MXene contents (3 mg, 7 mg, 10 mg, and 20 mg). The improved photocatalytic activity can be attributed to the high surface area as confirmed by a BET analysis and enhanced charge separation activity between CdS and Ti3C2 MXene.

Evaluation of axial length/total corneal refractive power ratio as a potential marker for ocular diagnosis of Marfan's syndrome in children.

AIM: To investigate whether the axial length (AL)/total corneal refractive power (TCRP) ratio is a sensitive and simple factor that can be used for the early diagnosis of Marfan's syndrome (MFS) in children. METHODS: The relationship between the AL/TCRP ratio and the diagnosis of MFS for 192 eyes in 97 children were evaluate. The biological characteristics, including age, sex, AL, and TCRP, were collected from medical records. Receiver operating characteristic (ROC) curve analysis was performed to investigate whether the AL/TCRP ratio effectively distinguishes MFS from other subjects. The Youden index was used to re-divide the whole population into two groups according to an AL/TCRP ratio of 0.59. RESULTS: Of 96 subjects (mean age 7.46±3.28y) evaluated, 56 (110 eyes) had a definite diagnosis of MFS in childhood based on the revised Ghent criteria, 41 (82 eyes) with diagnosis of congenital ectopia lentis (EL) were included as a control group. AL was negatively correlated with TCRP, with a linear regression coefficient of -0.36 (R 2=0.08). A significant correlation was found between age and the AL/TCRP ratio (P=0.023). ROC curve analysis showed that the AL/TCRP ratio distinguished MFS from the other patients at a threshold of 0.59. MFS patients were present in 24/58 (41.38%) patients with an AL/TCRP ratio of ≤0.59 and in 34/39 (87.18%) patients with an AL/TCRP ratio of >0.59. CONCLUSION: An AL/TCRP ratio of >0.59 is significantly associated with the risk of MFS. The AL/TCRP ratio should be measured as a promising marker for the prognosis of children MFS. Changes in the AL/TCRP ratio should be monitored over time.

Analysis of Axial Length in Young Patients with Marfan Syndrome and Bilateral Ectopia Lentis by Z-Scores.

INTRODUCTION: Marfan syndrome (MFS) is characterized by ectopia lentis (EL) and elongated axial length (AL). The characteristics of AL in young patients with MFS and bilateral EL before the lens surgery are not fully understood. METHODS: This study reviewed MFS patients under 20 years old with bilateral EL from January 2015 to October 2020. The Z-scores were introduced in terms of the number of standard deviations from the mean of age-matched normative data. Using Z-scores, the distribution of AL and influence factors were evaluated. The correlations between AL and other biometrics were analyzed. RESULTS: We reviewed 183 patients and enrolled both eyes. The mean age was 8.44 ± 4.69 years. About 36% of the patients were children under 6 years old. The median AL increased from 23.16 mm under 5 years old to 26.20 mm in the 16-20 age group, and when plotted, the trend presented a logarithmic curvature (R2 = 0.145, p < 0.001). The median Z-AL score was 1.24. One-third of eyes had Z-score <0. About 20% of the patients had AL difference over 1 mm between the right and left eyes, and the right one had longer Z-AL scores (p = 0.013). The eye complicated with megalocornea (10, 7.04%) had larger Z-AL scores (4.72 ± 3.51 vs. 1.10 ± 2.25, p = 0.002). A positive correlation was found between Z-AL and Z-corneal curvature radius (r = 0.265, p < 0.001). CONCLUSION: Young patients with bilateral EL but small AL should not be excluded from MFS without systematic examination. The age-adjusted Z-score will facilitate further study of the individual variations in AL across different ages.

Exosomes from adipose-derived stem cells attenuate UVB-induced apoptosis, ROS, and the Ca2+ level in HLEC cells.

Cartilage acid protein 1 (CRTAC1) encodes a protein containing the Ca2+binding domain, which can promote apoptosis of human lens epithelial cells (HLECs) induced by ultraviolet B radiation. Exosomes secreted from adipose-derived stem cells (ASC-exo) have been used to treat many diseases, but the effect of ASC-exo on cataracts has not been established. We hypothesized that ASC-exo has a therapeutic effect on cataracts by regulating CRTAC1. We established the UVB-induced injured HLECs model to test the interactions between CRTAC1 and miR-10a-5p, and the effect on the Ca2+ level and reactive oxygen species (ROS) generation in apoptotic HLECs. We found that UVB significantly increased the level of CRTAC1 expression and induced HLEC apoptosis, while ASC-exo inhibited the induction of UVB and exosome inhibitor reduced the inhibition of ASC-exo. The qRT-PCR results showed that miR-10a-5p had a low level of expression in cataract lesions, whereas CRTAC1 was highly expressed. There was a negative correlation between the expression of CRTAC1 and miR-10a-5p. ASC-exo reversed UVB-inhibited miR-10a-5p expression and miR-10a-5p negatively regulated CRTAC1. In vitro data showed that miR-10a-5p reversed UVB-induced ROS, apoptosis, and the Ca2+ level in HLECs. Overexpression of CRTAC1 reversed the induction of ASC-exo in UVB-injured HLECs, and low expression of CRTAC1 reversed the induction of miR-10a-5p inhibitor. By upregulating the level of miR-10a-5p expression and downregulating the level of CRTAC1 expression, exosomes from ASCs attenuated UVB-induced apoptosis, ROS generation, and the Ca2+ level in HLECs. Our research provides novel insight into the treatment methods and associated mechanisms underlying cataracts.

Down-regulation of CRTAC1 attenuates UVB-induced pyroptosis in HLECs through inhibiting ROS production.

Pyroptosis has been found to be related to diverse ocular diseases, including cataract. Abnormal CRTAC1 expression has been reported to involve in cataract formation by affecting cell apoptosis. Whether CRTAC1 regulates pyroptosis in the formation progress of cataract is completely unknown. Here, we aimed to investigate the regulatory effects of CRTAC1 on pyroptosis and the potential mechanism in the UVB-induced cell damage model. The results showed that the levels of the established pyroptosis markers (NLRP3, active Caspase-1, pro Caspase-1, GSDMD-N, IL-1ß and IL-18) were significantly increased in cataract patients. The above pyroptosis markers could be obviously induced by UVB-irradiation in human lens epithelial cells (HLECs), while down-regulation of CRTAC1 significantly reversed the UVB-induced pyroptosis. Up-regulation of CRTAC1 promoted HLECs pyroptosis, while the ROS inhibitor N-acetyl-l-cysteine blocked the effects of CRTAC1 overexpression. In conclusion, our findings further suggested that the prominent role of CRTAC1 in cataract formation.

NF-κB/Cartilage Acidic Protein 1 Promotes Ultraviolet B Irradiation-Induced Apoptosis of Human Lens Epithelial Cells.

The apoptosis of human lens epithelial cells (HLECs) is a characteristic change that occurs during the development of cataracts. Ultraviolet B (UVB) is known to induce the generation of reactive oxygen species (ROS) and apoptosis in HLECs, and thus cause cataracts. Previously, we reported the functions of cartilage acidic protein 1 (CRTAC1) in UVB-treated HLECs. However, the underlying mechanism was not known. In this study, we found that CRTAC1 expression and nuclear factor-kappa B (NF-κB) p65 nuclear translocation were elevated in capsule tissues of cataract patients in comparison with normal controls. The NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), alleviated UVB-induced apoptosis in HLECs; while activation of NF-κB suppressed the effects of the ROS inhibitor, N-acetyl-L-cysteine (NAC), on UVB-treated HLECs. The expression and promoter activity of CRTAC1 was inhibited by PDTC and NAC. Moreover, the suppressed effects of CRTAC1 knockdown on UVB-induced ROS generation, cell apoptosis, nuclear translocation of NF-κB p65, and p38 phosphorylation were attenuated by a p38 agonist. In contrast, the p38 inhibitor abolished the promotional effects of CRTAC1 overexpression on HLECs. Taken together, our results for the first time show that NF-κB is a potential transcription factor for CRTAC1. The regulatory network involving NF-κB, CRTAC1, and p38 may therefore play an important role in cataract formation.

A Review of Complicated Cataract in Retinitis Pigmentosa: Pathogenesis and Cataract Surgery.

Retinitis pigmentosa (RP) is a set of inherited retinal degenerative diseases that affect photoreceptor and retinal pigment epithelial cells (RPEs), possibly associated with some ocular complications, including cataract. The complicated cataract formation is most likely the result of RP-related inflammation response, and the most common morphology category is posterior subcapsular cataract (PSC). Despite the absence of curative pharmacologic treatment, phacoemulsification with intraocular lens implantation to deal with opacification in the lens is preferred due to the considerable visual outcomes. However, the incidence of intraocular and postoperative complications is higher in RP patients than those without, including intraoperative phototoxic retinal damage, posterior capsular opacification (PCO), capsular contraction syndrome (CCS), pseudophakic cystoid macular edema (PCME), increased postoperative intraocular pressure (IOP), and intraocular lens (IOL) dislocation. Hence, it needs much attention to surgery progress and close follow-up. In this review, we discuss the current understanding of RP patients with complicated cataracts from morphology to potential pathogenesis to cataract surgical procedure and provide a concise description and the recommended management of related surgery complications to broaden the knowledge and lower the latent risks to yield better clinical outcomes.

A literature review on Fuchs uveitis syndrome: An update.

Fuchs uveitis syndrome is a chronic, typically unilateral, ocular condition characterized by an asymptomatic mild inflammatory syndrome that can result in cataract and secondary glaucoma. Diagnosis is largely clinical because the etiology remains obscure. Fuchs uveitis syndrome is most likely the result of different insults or pathogenic mechanisms, including infections, autoimmune diseases, hereditary and sympathetic dysfunction. According to the infectious theory, the infection of herpes simplex virus, ocular toxoplasmosis, cytomegalovirus, rubella virus, and other viruses have been implicated in the pathogenesis of the disease. There is no indication for corticosteroid therapy in Fuchs patients, and treatment should be mostly reserved to cataract and glaucoma. Phacoemulsification with intraocular lens implantation is a safe procedure with good visual outcomes in patients with Fuchs uveitis syndrome. Glaucoma is often unresponsive to treatment and should actively be monitored both preoperatively and postoperatively in these patients. We discuss the current understanding of Fuchs uveitis syndrome from its clinical presentations through recommended management and provide a comprehensive description and the updated knowledge of its pathophysiology.

Management and Microbiological Characteristics of Membrane Formation on a Hydrophilic Acrylic Intraocular Lens: A Clinical Case Series and Material Comparative Study of Different IOLs.

Background/Aims. To report a case series of membrane formation on intraocular lenses (IOLs) after uneventful phacoemulsification and to evaluate the material characteristics and biofilm formation on different IOLs. Methods. Ten eyes implanted with the same type of IOLs were found to have membranes on their IOLs after uneventful phacoemulsification from May 2015 to May 2016. No other patients were found with the same phenomenon among 11236 patients who underwent cataract surgeries during this period. To further investigate the reasons for their formation, we assessed seven types of IOLs used in our hospital, including their material characteristics and the presence of microbes (Staphylococcus epidermidis) on the IOL surface by scanning electron microscopy (SEM). All IOLs were incubated under in vitro flow conditions (BioFlux 1000Z). After 36 h, the IOLs were taken from the system, and both the bound bacteria and biofilm formation were observed. Results. Five eyes underwent intravitreal injections of ceftazidime and norvancomycin with one positive culture obtained from the anterior chamber fluid. The other five eyes only received topical treatment of gatifloxacin/levofloxacin and tobramycin. At the last follow-up, all patients had best-corrected visual acuity (BCVA) of 20/50 or better. In the biofilm study on the IOL surface, Staphylococcus epidermidis biofilms formed more readily on hydrophilic acrylic IOLs than on hydrophobic acrylic IOLs. Conclusions. Bacterial adhesion and biofilm tend to develop on certain types of IOLs because of the characteristics of the biomaterial.

TRIM69 inhibits cataractogenesis by negatively regulating p53.

Ultraviolet B (UVB) irradiation can induce reactive oxygen species (ROS) production and apoptosis in human lens epithelial cells (HLECs), thus leading to the formation of cataracts. We studied the role of tripartite motif 69 (TRIM69) in cataract formation. The expression of TRIM69 protein was down-regulated in both human cataract capsule tissues and HLECs treated with UVB, whereas the expression of p53 protein exhibited an opposite trend. Ectopic expression of TRIM69 in HLECs significantly suppressed UVB-induced apoptosis and ROS production, whereas knockdown of TRIM69 promoted apoptosis and ROS production. TRIM69 can interact with p53 and induce its ubiquitination. The effects of TRIM69 overexpression in UVB-induced cell apoptosis and ROS production was clearly weakened by p53 overexpression, thus suggesting a role for p53 in TRIM69 functions. Furthermore, inhibition of ROS mitigated the effects of UVB irradiation on ROS production, cell apoptosis, forkhead box protein 3a (Foxo3a) phosphorylation, and TRIM69 expression. Additionally, Foxo3a overexpression significantly enhanced TRIM69 promoter activity, whereas Foxo3a knockdown had the opposite effect. In conclusion, we provide the first demonstration that Foxo3a is a potential transcription factor for TRIM69, and TRIM69 induces p53 ubiquitination. These results suggest that the Foxo3a/TRIM69/p53 regulatory network may be involved in cataract formation.

Neuroprotective effect of insulin-loaded chitosan nanoparticles/PLGA-PEG-PLGA hydrogel on diabetic retinopathy in rats.

BACKGROUND: To pursuit effective sustained release systems for insulin to treat diabetic retinopathy (DR), a novel insulin delivering system was developed via loading onto chitosan nanoparticles/poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid) hydrogel (ICNPH). METHODS AND MATERIALS: Examinations including electroretinography, HE staining, transmission electron microscopy, terminal deoxynucleotidyl transferased UTP nick-end labeling, immunofluorescence, Western blot, and real-time polymerase chain reaction were performed to evaluate the neuroprotective efficacy of ICNPH on DR by a single subconjunctival injection. RESULTS: Compared with the insulin, blank, and sham treatment groups, subconjunctival injection of ICNPH significantly reduced the decrease of scotopic B-wave amplitude, alleviated retinal micro- and ultrastructural changes, and reduced retinal cell apoptosis caused in DR rats. Meanwhile, a significant reduction of vascular endothelial growth factor and glial fibrillary acidic protein expression as well as a remarkable increase in Occludin expression was also found in retinas in ICNPH group compared with the sham treatment group. CONCLUSION: The results indicate that ICNPH has sufficient neuroprotective effect on retinas through subconjunctival injection in DR rats and facilitates controlled insulin delivery. It might be one of the therapeutic strategies for DR in the near future.

Cyclodialysis cleft repair and cataract management by phacoemulsification combined with internal tamponade using modified capsular tension ring insertion.

PURPOSE: To evaluate the surgical outcomes of cyclodialysis cleft repair and cataract management by phacoemulsification combined with internal tamponade using a modified capsular tension ring (MCTR) compared with direct cyclopexy. METHODS: The preoperative and postoperative characteristics of patients with cyclodialysis clefts who underwent surgery via insertion of an MCTR into the ciliary sulcus (MCTR group; 16 patients, 16 eyes) or direct cyclopexy (DC group; 16 patients, 16 eyes) were recorded. RESULTS: The cyclodialysis extended over 2.6 ± 1.9 clock hours in the MCTR group and 3.5 ± 1.8 clock hours in the DC group (P = 0.094). Postoperatively, the IOP was not significantly different between the MCTR and DC groups (12.9 ± 3.7 mmHg vs. 13.8 ± 6.2 mmHg, P = 0.985); the logarithm of the minimal angle of resolution BCVA was better (0.1 ± 0.2 vs. 1.0 ± 0.9, P < 0.001), and the anterior chamber depth was greater (3.87 ± 0.40 mm vs. 2.59 ± 0.58 mm, P < 0.001) in the MCTR group than in the DC group. Compared with the preoperative parameters, the postoperative BCVA, IOP, and anterior chamber depth values were significantly improved in the MCTR group (P < 0.05), whereas the BCVA showed no significant improvement postoperatively in the DC group (P = 0.174). Logistic regression revealed no significant risk factors for successful IOP control or BCVA improvement. CONCLUSION: Phacoemulsification combined with internal tamponade using MCTR insertion into the ciliary sulcus is a safe and minimally invasive method for effectively closing cyclodialysis clefts and managing cataract.

Metabolic characterization of human aqueous humor in the cataract progression after pars plana vitrectomy.

BACKGROUND: While pars plana vitrectomy (PPV) has become the third most commonly performed surgery in the world, it can also induce multiple post complications easily. Among them, cataract progression is the most frequent one that can lead to blindness eventually. METHODS: To understand the underlying mechanisms of post PPV cataract progression, we performed comprehensive metabolic characterization of aqueous humor (AH) samples from 20 cataract patients (10 post PPV complication and 10 none PPV cataract) by a non-targeted metabolomic analysis using gas chromatography combined with time-of-flight mass spectrometer (GC/TOF MS). RESULTS: A total of 263 metabolites were identified and eight of them are determined to be significantly different (VIP ≥ 1 and p ≤ 0.05) between post PPV group and none PPV control group. The significantly changed metabolites included glutaric acid and pelargonic acid that play key roles in the regulation of oxidative stress and inflammatory responses. Furthermore, we constructed a metabolic regulatory network in each group based on metabolite-metabolite correlations, which reveals key metabolic pathways and regulatory elements including amino acids and lipids metabolisms that are related to cataract progression. CONCLUSIONS: Altogether, this work discovered some potential metabolite biomarkers for post PPV cataract diagnostics, as well as casted some novel insights into the underlying mechanisms of cataract progression after PPV.