Clinicopathological features of corneal invasion by filtering bleb.

PURPOSE: To describe the clinicopathological characteristics and explore the possible etiology of cornea invasion by filtering bleb (CIFB) after filtering surgery. METHODS: We reviewed 22 patients treated for CIFB between March 2005 and March 2022. The patients were followed up for more than 1 year. Slit-lamp examination, optical coherence tomography (OCT), ultrasound biomicroscopy, and histopathological examination were performed to observe the morphology of the bleb and depth of corneal invasion. Depending on the severity of the lesion, treatments consisting of local massage, acupuncture separation, or surgical resection were administered. RESULTS: The mean age of the patients was 56.3 ± 8.8 years. All patients underwent filtering surgery in the moderate or advanced stage of glaucoma. The filtering bleb was closely connected with the cornea, and its posterior boundary was locally adhered. Forward displacement of the internal opening of the filtering bleb was found in 4 of 7 surgically treated patients. OCT and pathological examination showed that the filtering blebs invaded the corneal stroma. Removal of the adhesion of the posterior boundary of the filtering bleb by different treatment methods successfully improved the patients' conditions. CONCLUSION: Filtering blebs can invade the corneal stroma. Adhesion of the posterior boundary and forward displacement of the internal opening of the filtering bleb are the possible causes of CIFB. Removal of the adhesion of the posterior boundary of the filtering bleb can halt the progression of CIFB.

Exploring the Mechanism of the miRNA-145/Paxillin Axis in Cell Metabolism During VEGF-A-Induced Corneal Angiogenesis.

Purpose: Paxillin (PXN) is a key component of focal adhesions and plays an important role in angiogenesis. The aim of the present study was to investigate the effect of PXN in vascular endothelial growth factor A (VEGF-A)-induced angiogenesis in human umbilical vein endothelial cells (HUVECs). Methods: HUVECs were transfected with PXN overexpression and PXN interference vectors. Biochemical detection was used to detect adenosine triphosphate and lactic acid production. The morphology of mitochondria was observed under an electron microscope, and flow cytometry was conducted to measure mitochondrial membrane potential. Transwell experiments were used to detect the migration and tube formation ability of each group of cells. The expression of hexokinase (HK)1, HK2, glucose transporter 1 (GLUT1), phosphorylated phosphatidylinositol 3-kinase (PI3K), phosphorylated AKT, and phosphorylated mechanistic target of rapamycin (mTOR) was evaluated by western blot. Results: PXN silencing reduced the levels of lactic acid and adenosine triphosphate, downregulated HK1, HK2, and GLUT1, suppressed PI3K/AKT/mTOR signaling activation, and inhibited VEGF-A-induced mitochondria injury in VEGF-A-induced HUVECs. We also determined that miR-145-5p decreased the VEGF-A-induced expression of PXN and inhibited the invasion and angiogenesis of HUVECs. Also, miR-145-5p inhibition blocked the protective effect of PXN interference on VEGF-A-induced HUVEC injury. Furthermore, PXN interference significantly decreased lactic acid and adenosine triphosphate levels, inhibited PI3K/AKT/mTOR activation, and decreased the levels of HK1, HK2, and GLUT1 in VEGF-A-treated mouse corneal. Conclusions: The results indicate that PXN silencing inhibited the VEGF-A-induced invasion and angiogenesis of HUVECs via regulation of cell metabolism and mitochondrial damage, suggesting that PXN may be a potential target for antiangiogenic therapies.

The role of radiotherapy in pulmonary large cell neuroendocrine carcinoma: propensity score matching analysis.

The aim of the study was to investigate the survival advantage of radiotherapy (RT) in patients with pulmonary large cell neuroendocrine carcinoma (LCNEC). Patients with pulmonary LCNEC were extracted from the Surveillance, Epidemiology, and End Results (SEER) dataset between January 2004 and December 2013. Propensity score matching (PSM) analysis with 1:1 was used to ensure well-balanced characteristics of all comparison groups. A total of 1480 eligible cases were identified, with a median follow-up time of 11 months (0-131 months). After PSM, 980 patients were classified in no radiotherapy (No RT) and radiotherapy (RT) groups (n = 490 each). Patients in the RT group harbored significantly higher 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) rates compared to those in the No RT group (both P < 0.05). Furthermore, RT was an independent favorable prognostic factor of OS as well as CSS in multivariate analysis, both before [OS: hazard ratio (HR) 0.840, 95% confidence interval (CI) 0.739-0.954, P = 0.007; CSS: HR 0.847, 95% CI 0.741-0.967, P = 0.014] and after (OS: HR 0.854, 95% CI 0.736-0.970, P = 0.016; CSS: HR 0.848, 95% CI 0.735-0.978, P = 0.023) PSM. In subgroup analysis, American Joint Committee on Cancer (AJCC) stage II and III, tumor size 5-10 cm, patients who underwent no surgery, or patients who received chemotherapy could significantly benefit from RT (all P < 0.05). To sum up, our findings suggested that RT could prolong the survival of patients with pulmonary LCNEC, especially those with stage II and III, tumor size 5-10 cm, those with no surgery, or those who received chemotherapy.

Inhibition of EZH2 alleviates angiogenesis in a model of corneal neovascularization by blocking FoxO3a-mediated oxidative stress.

Enhancer of zeste homolog 2 (EZH2), a well-known methyltransferase, mediates histone H3 lysine 27 trimethylation (H3K27me3) and plays a vital role in ophthalmological disease. However, its role in corneal neovascularization (CoNV) remains unclear. In vitro and in vivo models were assessed in hypoxia-stimulated angiogenesis and in a mouse model of alkali burn-induced CoNV. Human umbilical vein endothelial cells (HUVECs) were cultured under hypoxic conditions and different reoxygenation times to identify the molecular mechanisms involved in this process. In this study, we found that EZH2 was positively related to corneal alkali burn-induced injury. Inhibition of EZH2 with 3-Deazaneplanocin A (DZNeP) alleviated corneal injury, including oxidative stress and neovascularization in vivo. Similarly, inhibition of EZH2 with either DZNeP or small interfering RNA (siRNA) exerted an inhibitory effect on hypoxia/reoxygenation (H/R)-induced oxidative stress and angiogenesis in HUVECs. Moreover, our study revealed that ablation of reactive oxygen species (ROS) with N-acetyl-cysteine suppressed angiogenesis in HUVECs exposed to H/R stimulation. Furthermore, Forkhead-box protein O3a (FoxO3a), which was positively associated with ROS production and angiogenesis, was elevated during H/R. This effect could be reversed through the suppression of the transcription activity of EZH2 with DZNeP or siRNA. In addition, the PI3K/Akt pathway, which is the upstream of FoxO3a, was activated in both DZNeP-treated mice and EZH2-inhibited HUVECs. Collectively, our results demonstrated that the inhibition of EZH2 alleviated corneal angiogenesis by inhibiting FoxO3a-dependent ROS production through the PI3K/Akt signaling pathway. These findings indicate that EZH2 may be a valuable therapeutic target for CoNV.

Orbital neuroblastoma metastasis: A case report and literature review.

RATIONALE: Neuroblastoma is one of the most common tumors found in children, and mostly arises in the adrenal gland and paravertebral regions. Orbital neuroblastoma metastasis is relatively rare, and is associated with poor prognosis. Since the symptoms and signs of orbital neuroblastoma are not specific, its diagnosis remains challenging. PATIENT CONCERNS: A 3-year-old girl presented with periorbital ecchymoses (raccoon eyes) and proptosis for 40 days. DIAGNOSES: Abdominal magnetic resonance imaging (MRI) and sonography analysis revealed a large mass in the left adrenal gland (primary tumor). The computed tomography and MRI further revealed multiple soft tissue masses in the skull and both orbits with erosion of the adjacent bones (the metastasis). The histological analysis of the tumor removed from the right orbit confirmed the diagnosis of neuroblastoma. INTERVENTIONS: The mass on the right face was surgically removed. OUTCOMES: The patient exhibited no deteriorative signs at the 6-month follow-up. LESSONS: Clinical manifestations, such as periorbital ecchymoses and proptosis, in combination with radiological analysis and histological findings, are important for the diagnosis of orbital neuroblastoma metastasis.

Protective effects of delphinidin against H2O2-induced oxidative injuries in human retinal pigment epithelial cells.

Age-related macular degeneration (AMD) is now one of the leading causes of blindness in the elderly population and oxidative stress-induced damage to retinal pigment epithelial (RPE) cells occurs as part of the pathogenesis of AMD. In the present study, we evaluated the protective effect of delphinidin (2-(3,4,5-trihydroxyphenyl) chromenylium-3,5,7-triol) against hydrogen peroxide (H2O2)-induced toxicity in human ARPE-19 cells and its molecular mechanism. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry demonstrated that pretreatment of ARPE-19 cells with delphinidin (25, 50, and 100 µg/ml) significantly increased cell viability and reduced the apoptosis from H2O2 (0.5 mM)-induced oxidative stress in a concentration-dependent manner, which was achieved by the inhibition of Bax, cytochrome c, and caspase-3 protein expression and enhancement of Bcl-2 protein. The same tendency was observed in ARPE-19 cells pre-treated with 15 mM of N-acetylcysteine (NAC) before the addition of H2O2 Furthermore, pre-incubation of ARPE-19 cells with delphinidin markedly inhibited the intracellular reactive oxygen species (ROS) generation and Nox1 protein expression induced by H2O2 Moreover, the decreased antioxidant enzymes activities of superoxide dismutase (SOD), catalase (CAT), and glutathione-peroxidase (GSH-PX) and elevated (MDA) level in H2O2-treated cells were reversed to the normal standard by the addition of delphinidin, which was regulated by increasing nuclear Nrf2 protein expression in ARPE-19 cells. Our results suggest that delphinidin effectively protects human ARPE-19 cells from H2O2-induced oxidative damage via anti-apoptotic and antioxidant effects.

Modulation of Corneal FAK/PI3K/Akt Signaling Expression and of Metalloproteinase-2 and Metalloproteinase-9 during the Development of Herpes Simplex Keratitis.

To observe the expression of MMP-2 and MMP-9 and of the FAK/PI3K/Akt signaling pathway in HSK. Fifty BALB/c mice were infected to establish the model and killed on days 0, 2, 7, 14, and 28. The cornea samples were prepared, respectively. Slit lamp examination, immunofluorescence staining, reverse transcription PCR, and Western blot were used to detect the index. After HSV-1 infection, different degrees of epithelial or stromal damage and corneal opacity were observed. Immunofluorescence staining showed that the expressions of MMP-2 and MMP-9 at different levels of corneal tissue were observed on the 0d, 2d, 7d, 14d, and 28d. Compared with 0d, the relative expression levels of MMP-2 and MMP-9 mRNA at 2d, 7d, 14d, and 28d were significantly increased (all P< 0.05). Compared with 14d, the relative expression of MMP-2 and MMP-9 mRNA decreased on the 2d, 7d, and 28d (all P< 0.05). Western blot showed that the protein expressions of p-FAK, p-PI3K, p-Akt, MMP-2, and MMP-9 at 2d, 14d, and 28d were all significantly higher than 0d (all P< 0.05). At 14 d, the expressions of p-FAK, p-PI3K, p-Akt, and MMP-2 were significantly higher than those at 2d, 7d, and 28d (all P< 0.05). The protein expression of FAK, PI3K, and Akt in corneal of mice in each time period had no significant (all P> 0.05). These data suggest that FAK/PI3K/Akt signaling pathway and MMP-2 and MMP-9 may be involved in the development of HSK.

Torsional and burst mode phacoemulsification for patients with hard nuclear cataract: A randomized control study.

This article aims to evaluate the outcomes of torsional and burst mode phacoemulsification in hard nuclear cataracts.Eighty eyes with grade IV or V nuclear opalescence were treated with phacoemulsification and intraocular lens implantation using conventional mode (Group A, n = 40) or torsional and burst mode phacoemulsification (Group B, n = 40). For good visualization of anterior capsule, trypan blue was injected to the anterior chamber before continuous circular capsulorhexis. The mean cumulative dissipated energy and ultrasound time were recorded. The best-corrected visual acuity, endothelial cell density, and central corneal thickness were measured before and at 1 month after surgery.The cumulative dissipated energy and ultrasound time of Group B were significantly less than that of Group A. The postoperative best-corrected visual acuities of the 2 groups were comparable. At 1 month after surgery, the changes in the endothelial cell density were significantly greater in Group A than in Group B, and the changes in the central corneal thickness were not significantly different between the 2 groups.Torsional and burst mode is a safe and effective surgical method for treating hard cataracts.

Risk Factors for Dry Eye Syndrome: A Retrospective Case-Control Study.

PURPOSE: To investigate the independent risk factors of dry eye syndrome (DES) in Chinese. METHODS: A hospital-based age- and sex-matched population was enrolled with a case-control ratio of 1:2, with 789 DES case patients and 1119 healthy family members. Both groups underwent standard ophthalmologic examinations, including slit-lamp evaluation of the anterior segment, measurement of tear film breakup time, Schirmer test, and corneal fluorescein staining. Data on demographic characteristics and lifestyle habits were collected using a questionnaire. Dry eye syndrome risk factors were identified by univariate and multivariate logistic regression analyses. RESULTS: The following independent risk factors showed significant association with DES: diabetes (odds ratio [OR], 1.408; 95% confidence interval [CI], 1.031 to 1.924), hepatitis C (OR, 3.326; 95% CI, 1.632 to 6.776); connective tissue disease (OR, 2.157; 95% CI, 1.679 to 2.771), benign prostatic hyperplasia (OR, 3.892; 95% CI, 2.476 to 6.116), rosacea (OR, 3.747; 95% CI, 1.972 to 7.120), posttraumatic stress disorder (OR, 1.449; 95% CI, 1.043 to 2.013), hematopoietic stem cell transplantation (OR, 7.269; 95% CI, 2.312 to 22.849), head and neck radiotherapy (OR, 8.776; 95% CI, 3.096 to 24.873), postmenopausal estrogen therapy (OR, 1.912; 95% CI, 1.160 to 3.151), antihistamines (OR, 2.040; 95% CI, 1.516 to 2.746), antidepressants (OR, 1.982; 95% CI, 1.077 to 3.647), contact lenses (OR, 2.366; 95% CI, 1.266 to 4.423), and video display terminal exposure for more than 6 h/d (OR, 2.275; 95% CI, 1.451 to 3.568). Potentially protective factors against DES were vitamin supplements (OR, 0.716; 95% CI, 0.528 to 0.972) and Ω-3 fatty acid-rich diet (OR, 0.514; 95% CI, 0.332 to 0.796). CONCLUSION: Several known risk factors of DES are applicable to Chinese, and some distinctive dietary factors may be protective in this population.

Paxillin regulates vascular endothelial growth factor A-induced in vitro angiogenesis of human umbilical vein endothelial cells.

The purpose of the present study was to investigate the role of paxillin in the vascular endothelial growth factor A (VEGF­A)­induced adhesion, proliferation, migration and capillary formation of endothelial cells (ECs) in vitro. Human umbilical vein ECs (HUVECs) were used to evaluate these four processes in vitro. The HUVECs were either mock­transfected (control), transfected with scramble small interference RNA (siRNA) or transfected with siRNA specifically targeting paxillin. VEGF­A (20 ng/ml) was used to stimulate angiogenesis. The VEGF­A treatment significantly increased the adhesion, proliferation, migration and tube formation of the HUVECs in the control and scramble siRNA groups, whereas the siRNA­-mediated knockdown of paxillin inhibited these VEGF­A­induced effects. Paxillin is essential for VEGF­A­mediated angiogenesis in ECs and its inhibition may be a potential target for antiangiogenic therapies.

[Effects of focal adhesional kinase signaling on TNF-α induced gelatinases activity in cornea epithelium].

OBJECTIVE: To investigate the effect of focal adhesional kinase (FAK) on tumor necrosis factor α (TNF-α)-induced MMP-2 and -9 activities in cornea epithelium. METHODS: Experimental research. The human corneal epithelial cells (HCE) were cultured in vitro. HCEs were incubated with different concentrations of TNF-α for 24 h, including 1 µg/L (group B), 10 µg/L (group C) and 100 µg/L (group D). The control group (group A) was incubated with phosphate buffer solution. The activities of MMPs were examined by gelatin zymography and the phosphorylation of FAK was examined by western blot analysis. FAK was down regulated by FAK siRNA following lipofectamine-mediated transfection in corneal epithelial cells. Down-regulation was confirmed using western blot analysis. Cells cultured with different concentrations of TNF-α (Groups B to D) and the control group (group A) was at similar volumes of media. Then the activities of MMP-2 and -9 were examined by gelatin zymography and the phosphorylation of FAK by western blot analysis. Statistical methods adopted one-way ANOVA and Tukey's honestly significant test between each group. RESULTS: Gelatin zymography: Activities of MMP-2 and -9 in TNF-α treated groups were greater than those of the control group. The activity of MMP-2 in A, B, C and D groups was 124.06 ± 4.06, 146.72 ± 5.51, 241.18 ± 5.65 and 389.95 ± 4.44, respectively with F = 2960.91, P = 0.000. The activity of MMP-9 in A, B, C and D groups was 122.78 ± 5.86, 165.70 ± 7.90, 479.49 ± 6.22 and 495.88 ± 5.03 (F = 4937.46, P = 0.000). Significant differences were found in each two groups (P = 0.000). Western blot analysis:the phosphorylation of FAK (p-FAK) in test groups (10-100 ng/ml) were significantly greater than that in control group (p-FAK of group C and D was 0.52 ± 0.03 and 0.61 ± 0.06, F = 431.03, P = 0.000). p-FAK levels in 100 ng/ml group were greater than that in 10 ng/ml group (P = 0.005). After down-regulating the protein FAK, TNF-α had no effect on the activity of MMP-2 (The data of MMP-2 were 55.13 ± 0.66, 55.67 ± 0.43, 55.49 ± 0.20 and 55.91 ± 0.37 in groups A, B, C and D, F = 2.73, P = 0.079). We detected the increasing activity of MMP-9 in group C, D and p-FAK in group D (The data of MMP-9's activity were 80.48 ± 0.39, 81.26 ± 0.62, 84.43 ± 0.47, 85.56 ± 0.61 in groups A, B, C and D, F = 105.80, P = 0.000). The activity of MMP-9 in group D was stronger than that from the group C (P = 0.019). We just only detected a small quantity of p-FAK in group D (0.47 ± 0.05), which was weaker than that before down regulating the protein FAK (t = 5.03, P = 0.001). CONCLUSION: Our results demonstrate the critical role of FAK in TNF-α induced activity of MMP-2 and -9 in human corneal epithelium cells. Blocking the FAK signaling pathway can reduce the activity of MMP-2 and -9 which may play an important role in prevention and treatment of corneal diseases.