Beneficial Impact of Eicosapentaenoic Acid on the Adverse Effects Induced by Palmitate and Hyperglycemia on Healthy Rat Chondrocyte.

Osteoarthritis (OA) is the most prevalent form of arthritis and a major cause of pain and disability. The pathology of OA involves the whole joint in an inflammatory and degenerative process, especially in articular cartilage. OA may be divided into distinguishable phenotypes including one associated with the metabolic syndrome (MetS) of which dyslipidemia and hyperglycemia have been individually linked to OA. Since their combined role in OA pathogenesis remains to be elucidated, we investigated the chondrocyte response to these metabolic stresses, and determined whether a n-3 polyunsaturated fatty acid (PUFA), i.e., eicosapentaenoic acid (EPA), may preserve chondrocyte functions. Rat chondrocytes were cultured with palmitic acid (PA) and/or EPA in normal or high glucose conditions. The expression of genes encoding proteins found in cartilage matrix (type 2 collagen and aggrecan) or involved in degenerative (metalloproteinases, MMPs) or in inflammatory (cyclooxygenase-2, COX-2 and microsomal prostaglandin E synthase, mPGES) processes was analyzed by qPCR. Prostaglandin E2 (PGE2) release was also evaluated by an enzyme-linked immunosorbent assay. Our data indicated that PA dose-dependently up-regulated the mRNA expression of MMP-3 and -13. PA also induced the expression of COX-2 and mPGES and promoted the synthesis of PGE2. Glucose at high concentrations further increased the chondrocyte response to PA. Interestingly, EPA suppressed the inflammatory effects of PA and glucose, and strongly reduced MMP-13 expression. Among the free fatty acid receptors (FFARs), FFAR4 partly mediated the EPA effects and the activation of FFAR1 markedly reduced the inflammatory effects of PA in high glucose conditions. Our findings demonstrate that dyslipidemia associated with hyperglycemia may contribute to OA pathogenesis and explains why an excess of saturated fatty acids and a low level in n-3 PUFAs may disrupt cartilage homeostasis.

The effect of ET1-CTGF mediated pathway on the accumulation of extracellular matrix in the trabecular meshwork and its contribution to the increase in IOP.

PURPOSE: To investigate the effect of endothelin-1 (ET-1) in excessive accumulation of extracellular matrix (ECM) of the trabecular meshwork (TM) and its role in intraocular pressure (IOP) regulation. METHODS: Cultured human TM cells (HTMCs) were treated with ET-1, ET-1 + ETA receptor (ETAR) antagonist BQ123, ET-1 + ETB receptor (ETBR) antagonist BQ788. The expressions of fibronectin (FN) and collagen type IV (Col IV) were evaluated by western blotting and immunofluorescence. A time course effect of ET-1 on the transcription level of connective tissue growth factor (CTGF) was investigated by qRT-PCR. Next, the transcription level of CTGF was downregulated by using antisense oligodeoxynucleotide sequence. Then HTMCs were treated with ET-1, and the expression levels of FN and Col IV were evaluated by western blotting. In addition, by using an ex-vivo model of cultured anterior eye segment, we explored the effect of ET-1 on IOP changes and the expressions of FN and Col IV. RESULTS: In cultured HTMCs, the expressions of FN and Col IV were significantly increased after ET-1 treatment, which were blocked by the pretreatment of ETAR antagonist BQ123, rather than ETBR antagonist BQ788. Besides, the CTGF mRNA level increased significantly and reached a peak after 48 h of ET-1 treatment. However, the effect of ET-1 on increasing the expressions of FN and Col IV in HTMCs could be inhibited by the downregulation of CTGF. In an ex-vivo model, IOP increased significantly after ET-1 administration, which could be blocked by BQ123 but not by BQ788. Furthermore, elevated expressions of FN and Col IV in TM were observed after ET-1 perfusion, and could be inhibited by BQ123 pretreatment. CONCLUSION: Excessive ET-1 in aqueous humor could lead to the abnormal accumulation of FN and Col IV in TM via the ETA-CTGF pathway, thereby increasing IOP.

Corrigendum: Effects and potential mechanisms of exercise and physical activity on eye health and ocular diseases.

[This corrects the article DOI: 10.3389/fmed.2024.1353624.].

Effects and potential mechanisms of exercise and physical activity on eye health and ocular diseases.

In the field of eye health, the profound impact of exercise and physical activity on various ocular diseases has become a focal point of attention. This review summarizes and elucidates the positive effects of exercise and physical activities on common ocular diseases, including dry eye disease (DED), cataracts, myopia, glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD). It also catalogues and offers exercise recommendations based on the varying impacts that different types and intensities of physical activities may have on specific eye conditions. Beyond correlations, this review also compiles potential mechanisms through which exercise and physical activity beneficially affect eye health. From mitigating ocular oxidative stress and inflammatory responses, reducing intraocular pressure, enhancing mitochondrial function, to promoting ocular blood circulation and the release of protective factors, the complex biological effects triggered by exercise and physical activities reveal their substantial potential in preventing and even assisting in the treatment of ocular diseases. This review aims not only to foster awareness and appreciation for how exercise and physical activity can improve eye health but also to serve as a catalyst for further exploration into the specific mechanisms and key targets through which exercise impacts ocular health. Such inquiries are crucial for advancing innovative strategies for the treatment of eye diseases, thereby holding significant implications for the development of new therapeutic approaches.

Irisin attenuates acute glaucoma-induced neuroinflammation by activating microglia-integrin αVß5/AMPK and promoting autophagy.

Neuroinflammation, characterized by microglial activation and the release of multiple inflammatory mediators, is a key factor in acute glaucomatous injury leading to retinal ganglion cell (RGC) death and ultimately irreversible vision loss. Irisin, a novel exercise-induced myokine, has demonstrated anti-inflammatory activity in ischemia/reperfusion injuries across multiple organs and has displayed a significant neuroprotective role in experimental stroke disease models. This study examined the protective impact of irisin and investigated its potential mechanism involved in this process utilizing an acute ocular hypertension (AOH)-induced retinal injury model in mice and a microglia inflammation model induced by lipopolysaccharide (LPS). There was a transient downregulation of irisin in the retina after AOH injury, with parallel emergence of retinal neuroinflammation and RGC death. Irisin attenuated retinal and optic nerve damage and promotes the phenotypic conversion of microglia from M1 to M2. Mechanistically, irisin significantly upregulated the expression of integrin αVß5, p-AMPK, and autophagy-related markers. Integrin αVß5 was highly expressed on microglia but hardly expressed on RGC. The integrin αVß5 inhibitor cilengitide, the AMPK inhibitor dorsomorphin, and the autophagy inhibitor 3-Methyladenine (3-MA) blocked the neuroprotective effects of irisin. Our results suggest irisin attenuates acute glaucoma-induced neuroinflammation and RGC death by activating integrin αVß5/AMPK in microglia and promoting autophagy. It should be considered a potential neuroprotective therapy for acute glaucoma.

Changes to Outflow Structures After Pilocarpine in Primary Open Angle Glaucoma Compared With Healthy Individuals Using Optical Coherence Tomography.

PRCIS: Lower response of aqueous outflow pathway structures after pilocarpine could be observed in primary open angle glaucoma (POAG) patients, which is likely to be helpful for understanding intraocular pressure (IOP) evaluation in glaucoma. PURPOSE: To evaluate the morphologic changes in the trabecular meshwork (TM), Schlemm canal (SC), scleral spur (SS), and ciliary muscle after miosis in patients with POAG and healthy individuals. METHODS: A total of 30 patients with POAG and 26 healthy controls were recruited. All participants underwent complete ophthalmologic examinations, including IOP and swept-source optical coherence tomography (OCT), before and 1 hour after the local administration of pilocarpine (2%). OCT measurements included TM thickness and width, SC diameter and area, SS length, ciliary muscle thickness, and ciliary muscle angle (CMA). RESULTS: Pilocarpine administration induced a decline in IOP (15.6±2.3-14.6±2.2 mm Hg), decrease in nasal SS length (196.31±47.75-171.52±33.93 µm), decrease in TM thickness (90.18±16.43-83.02±13.74 µm), and increase in SC diameter (134.84±32.28-162.08±48.67 µm) and SC area (3851.37±1455.07-4801.39±1762.37 µm 2 ) among healthy controls. In contrast, no significant changes in IOP and OCT measurements were found in patients with POAG. At baseline, CMA was independently correlated with IOP in normal eyes. After miosis, the change in TM thickness was independently correlated with changes in IOP in normal eyes; in eyes with POAG, changes in SS length and CMA were independently associated with changes in IOP. CONCLUSIONS: Topical pilocarpine-induced morphologic changes to outflow pathway structures in healthy individuals without significant changes in POAG. The lower response observed in patients with glaucoma may be relevant to understanding IOP changes.

In vivo quantification of human aqueous veins by enhanced depth imaging optical coherence tomography and optical coherence tomography angiography images.

AIM: To investigate the aqueous vein in vivo by using enhanced depth imaging optical coherence tomography (EDI-OCT) and optical coherence tomography angiography (OCTA). METHODS: In this cross-sectional comparative study, 30 healthy participants were enrolled. Images of the aqueous and conjunctival veins were captured by EDI-OCT and OCTA before and after water loading. The area, height, width, location depth and blood flow of the aqueous vein and conjunctival vein were measured by Image J software. RESULTS: In the static state, the area of the aqueous vein was 8166.7±3272.7 µm2, which was smaller than that of the conjunctival vein (13 690±7457 µm2, P<0.001). The mean blood flow density of the aqueous vein was 35.3%±12.6%, which was significantly less than that of the conjunctival vein (51.5%±10.6%, P<0.001). After water loading, the area of the aqueous vein decreased significantly from 8725.8±779.4 µm2 (baseline) to 7005.2±566.2 µm2 at 45min but rose to 7863.0±703.2 µm2 at 60min (P=0.032). The blood flow density of the aqueous vein decreased significantly from 41.2%±4.5% (baseline) to 35.4%±3.2% at 30min but returned to 45.6%±3.6% at 60min (P=0.021). CONCLUSION: The structure and blood flow density of the aqueous vein can be effectively evaluated by OCT and OCTA. These may become biological indicators to evaluate aqueous vein changes and aqueous outflow resistance under different interventions in glaucoma patients.

Stimulation of Liver Fibrosis by N2 Neutrophils in Wilson's Disease.

BACKGROUND & AIMS: Wilson's disease is an inherited hepatoneurologic disorder caused by mutations in the copper transporter ATP7B. Liver disease from Wilson's disease is one leading cause of cirrhosis in adolescents. Current copper chelators and zinc salt treatments improve hepatic presentations but frequently worsen neurologic symptoms. In this study, we showed the function and machinery of neutrophil heterogeneity using a zebrafish/murine/cellular model of Wilson's disease. METHODS: We investigated the neutrophil response in atp7b-/- zebrafish by live imaging, movement tracking, and transcriptional analysis in sorted cells. Experiments were conducted to validate liver neutrophil heterogeneity in Atp7b-/- mice. In vitro experiments were performed in ATP7B-knockout human hepatocellular carcinomas G2 cells and isolated bone marrow neutrophils to reveal the mechanism of neutrophil heterogeneity. RESULTS: Recruitment of neutrophils into the liver is observed in atp7b-/- zebrafish. Pharmacologic stimulation of neutrophils aggravates liver and behavior defects in atp7b-/- zebrafish. Transcriptional analysis in sorted liver neutrophils from atp7b-/- zebrafish reveals a distinct transcriptional profile characteristic of N2 neutrophils. Furthermore, liver N2 neutrophils also were observed in ATP7B-knockout mice, and pharmacologically targeted transforming growth factor ß1, DNA methyltransferase, or signal transducer and activator of transcription 3 reduces liver N2 neutrophils and improves liver function and alleviates liver inflammation and fibrosis in ATP7B-knockout mice. Epigenetic silencing of Socs3 expression by transforming growth factor ß1 contributes to N2-neutrophil polarization in isolated bone marrow neutrophils. CONCLUSIONS: Our findings provide a novel prospect that pharmacologic modulation of N2-neutrophil activity should be explored as an alternative therapeutic to improve liver function in Wilson's disease.

Comparative efficacy of 5 sodium-glucose cotransporter protein-2 (SGLT-2) inhibitor and 4 glucagon-like peptide-1 (GLP-1) receptor agonist drugs in non-alcoholic fatty liver disease: A GRADE-assessed systematic review and network meta-analysis of randomized controlled trials.

Background: The relative efficacy of 5 sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and 4 glucagon-like peptide-1 (GLP-1) receptor agonists for non-alcoholic fatty liver disease (NAFLD) therapy has not been sufficiently investigated. Methods: Randomized controlled trials (RCTs) in which patients with NAFLD were treated with SGLT-2 inhibitors or GLP-1 receptor agonists were included. Primary outcomes were improvements in liver enzymes and liver fat parameters, while secondary outcomes included anthropometric measures, blood lipids and glycemic parameters. The frequentist method was used to perform a network meta-analysis. Evidence certainty was assessed using the grading of recommendations assessment, development, and evaluation (GRADE). Results: The criteria were satisfied by 37 RCTs with 9 interventions (5 SGLT-2 inhibitors and 4 GLP-1 receptor agonists). Based on high certainty evidence, in patients with NAFLD (or comorbid with type 2 diabetes), semaglutide could lower alanine aminotransferase as well as aspartate aminotransferase, γ-glutamyl transferase, controlled attenuation parameter, liver stiffness measurement, body weight, systolic blood pressure, triglycerides, high-density lipoprotein-cholesterol, glycosylated hemoglobin. Liraglutide could lower alanine aminotransferase as well as subcutaneous adipose tissue, body mass index, fasting blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment, while dapagliflozin could lower alanine aminotransferase as well as body weight, fasting blood glucose, postprandial blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment. Conclusion: Semaglutide, liraglutide, and dapagliflozin all have a certain effect on NAFLD (or comorbid with type 2 diabetes) based on high confidence evidence from indirect comparisons, and semaglutide appears to have a therapeutic advantage over the other included medicines. Head-to-head studies are needed to provide more confidence in clinical decision-making.

Comparative efficacy of glucagon-like peptide 1 (GLP-1) receptor agonists, pioglitazone and vitamin E for liver histology among patients with nonalcoholic fatty liver disease: systematic review and pilot network meta-analysis of randomized controlled trials.

INTRODUCTION: There is no conclusive evidence comparing the efficacy of glucagon-like peptide 1 (GLP-1) receptor agonists to the other guidelines recommended pharmacotherapy for nonalcoholic fatty liver disease (NAFLD). Therefore, we aim to compare the effects of GLP-1 receptor agonists, pioglitazone and vitamin E in patients with NAFLD. METHODS: We searched PubMed, Embase, Web of Science and Cochrane Library up to 11 April 2022. Randomized clinical trials (RCTs) comparing GLP-1 receptor agonists, pioglitazone and vitamin E against placebo or other active controls in patients with NAFLD were included. RESULTS: Nine RCTs including 1482 patients proved eligible. GLP-1 receptor agonists ranked first in steatosis, ballooning necrosis, γ-glutamyl transferase, body weight, body mass index, and triglycerides. Administration of GLP-1 receptor agonists, as compared with placebo, was associated with improvement in liver histology [steatosis (OR = 4.11, 95% CI: 2.83, 5.96), ballooning necrosis (OR = 3.07, 95% CI: 2.14, 4.41), lobular inflammation (OR = 1.86, 95% CI: 1.29, 2.68), fibrosis (OR = 1.52, 95% CI: 1.06, 2.20)]. CONCLUSIONS: GLP-1 receptor agonists were as effective as pioglitazone and vitamin E for liver histology among patients with NAFLD. GLP-1 receptor agonists might be considered as an alternative or complementary treatment in the future clinical practice. [Figure: see text].

Effects of dapagliflozin in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Dapagliflozin as a treatment option in patients with nonalcoholic fatty liver disease (NAFLD) has received increasing attention, however, the efficacy and safety of dapagliflozin for NAFLD has not been well assessed. This meta-analysis aimed to summarize these RCTs and evaluate the efficacy of dapagliflozin for patients with NAFLD. METHODS: The PubMed, Embase, Web of Science, and Cochrane Library databases were searched for RCTs comparing dapagliflozin with placebo or active comparator in patients with NAFLD from inception to Oct 2021. RESULTS: We included seven trials with 390 randomized participants in total. Compared to the placebo or control group, dapagliflozin could reduce the levels of alanine aminotransferase(ALT) (WMD: -6.62U/L; 95%CI: -12.66,-0.58; p = 0.03) and aspartate aminotransaminase(AST) (WMD: -4.20U/L; 95%CI: -7.92,-0.47; p = 0.03). However, dapagliflozin produced a non-significant decrease in gamma-glutamyl transferase (GGT) levels (WMD: -7.28U/L; 95%CI: -16.26,1.71; p = 0.11). Additionally, we showed that dapagliflozin significantly affect Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (WMD: -0.88; 95%CI: -1.43,-0.33; p = 0.002). Metabolic outcomes, such as bodyweight (WMD: -3.79 Kg; 95%CI: -4.63,-2.95; p < 0.00001), body mass index (BMI) (WMD: -1.33 Kg/m2; 95%CI: -2.37,-0.28; p = 0.01), low-density lipoprotein cholesterol (LDL-C) (WMD: -2.66 mg/dL; 95%CI: -3.99,-1.32; p < 0.00001) and triglycerides (TG) (WMD: -16.77 mg/dL; 95%CI: -31.93,-1.61; p = 0.03) were also reduced. Meanwhile, we found that dapagliflozin increased total cholesterol (TC) (WMD: 9.77 mg/dL; 95%CI: 1.58,17.97; p = 0.02). There was no significant difference in the incidence of total adverse events between the dapagliflozin group and the control group (RR = 0.96; 95%CI: 0.60,1.54; p = 0.86). CONCLUSION: Our results suggest that dapagliflozin effectively improves liver function parameters and metabolic outcomes among patients with NAFLD. At the same time, treatment with dapagliflozin may increase total cholesterol.

Deep learning-based classification of the anterior chamber angle in glaucoma gonioscopy.

In the proposed network, the features were first extracted from the gonioscopically obtained anterior segment photographs using the densely-connected high-resolution network. Then the useful information is further strengthened using the hybrid attention module to improve the classification accuracy. Between October 30, 2020, and January 30, 2021, a total of 146 participants underwent glaucoma screening. One thousand seven hundred eighty original images of the ACA were obtained with the gonioscope and slit lamp microscope. After data augmentation, 4457 images are used for the training and validation of the HahrNet, and 497 images are used to evaluate our algorithm. Experimental results demonstrate that the proposed HahrNet exhibits a good performance of 96.2% accuracy, 99.0% specificity, 96.4% sensitivity, and 0.996 area under the curve (AUC) in classifying the ACA test dataset. Compared with several deep learning-based classification methods and nine human readers of different levels, the HahrNet achieves better or more competitive performance in terms of accuracy, specificity, and sensitivity. Indeed, the proposed ACA classification method will provide an automatic and accurate technology for the grading of glaucoma.

Analogs of microgravity: the function of Schlemm's canal, intraocular pressure and autonomic nervous during the head-down tilt test in healthy subjects.

AIM: To evaluate the ocular outcomes and to elucidate possible mechanisms underlying intraocular pressure (IOP) change following the head-down tilt (HDT) test. METHODS: The study included 21 participants at the Department of Ophthalmology of Tongji Hospital. Subjects received the test of I-care tonometry, enhanced depth imaging optical coherence tomography and heart rate variability (HRV) analysis before and after 15min HDT test. The lumen area of Schlemm's canal (SCAR), IOP, HRV were calculated. RESULTS: IOP increased significantly after 20° head down position from 14.0±3.0 to 17.0±3.3 mm Hg (P<0.001). SCAR decreased from 13449.0±5454.9 µm2 at sitting condition to 9576.6±4130.9 µm2 post 15min HDT test. High frequency (HF) indices increased significantly from 1462±865 Hz at baseline to 2128±824 Hz. Heart rate (HR) decreased significantly from 76±11.48 to 70±11.52 bpm after the HDT. The linear regression analysis showed that the difference of HF and SCAR significantly correlated with each other during the HDT (R2 =20%, P=0.04). CONCLUSION: These outcomes perform the first evidence of the activation of autonomic nervous system of HDT may cause the collapse of Schlemm's canal lumen, which in turn leading to the increased IOP.

Quantitative analysis of internal components of the human crystalline lens during accommodation in adults.

To quantitatively analyze changes in the inner components of the human crystalline lens during accommodation in adults. Eyes of 23 subjects were sequentially examined using CASIA2 Optical Coherence Tomography under 0D, - 3D and - 6D accommodation states. The anterior chamber depth (ACD), anterior and posterior crystalline lens radius of the curvature (ALRC and PLRC) were obtained using built-in software. The lens thickness (LT), lenticular nucleus thickness (NT), anterior cortex thickness (ACT), posterior cortex thickness (PCT), anterior and posterior lenticular nucleus radius of the curvature (ANRC and PNRC), anterior and posterior lenticular nucleus vertex (ANV and PNV) were quantified manually with the Image-pro plus software. During accommodation, the ACD became significantly shallower and LT significantly increased. For changes in the lens, the ALRC decreased by an average magnitude (related to accommodative stimuli) 0.44 mm/D, and PLRC decreased 0.09 mm/D. There was no difference for the ACT and PCT in different accommodation states. For lenticular nucleus response, NT increased on average by 30 µm/D. Both the ANRC and PNRC decreased on average by 212 µm/D and 115 µm/D respectively. The ANV moved forward on average by 0.07 mm under - 3D accommodative stimuli and 0.16 mm for - 6D. However, there was no statistically significant difference between different accommodation states in the PNV movement. Under accommodation stimulation, lens thickness changed mainly due to the lenticular nucleus, but not the cortex. For the lenticular nucleus, both the ANRC and PNRC decreased and ANRC changed the most. The anterior surface of the nucleus moved forward while the posterior surface of the nucleus moved backward but only slightly.

Investigation of SARS-CoV-2 on Ocular Surface of Coronavirus Disease 2019 Patients Using One-Step Reverse-Transcription Droplet Digital PCR.

PURPOSE: This study detects SARS-CoV-2 in the ocular surface through one-step reverse-transcription droplet digital PCR (one-step RT-ddPCR) and evaluates the possibility of the ocular surface as a possible transmission route. METHODS: A single-center prospective observational study was designed to investigate the viral loads in ocular surface. Specimens including the conjunctival swabs, nasopharyngeal swabs and blood were synchronously collected at a single time point for all COVID-19 patients. SARS-CoV-2 loads in nasopharyngeal swabs were tested by real-time polymerase chain reaction (PCR); the blood samples and conjunctival swabs were tested by real-time PCR and one-step RT-ddPCR. RESULTS: Sixty-eight COVID-19 patients confirmed by nasopharyngeal real-time PCR were recruited. In the single time point test, 40 cases showed positive SARS-CoV-2 detection in either the blood, tears, or nasopharynx, of which four cases were triple-positive, 10 were dual-positive, and 26 were single-positive. The positive rate of nasopharyngeal swab real-time PCR test was 22.1% (15/68). The positive rate of blood and conjunctival swabs by one-step RT-ddPCR was 38.2% (26/68) and 25% (17/68), respectively, whereas real-time PCR was all negative. Positive conjunctival swabs were significantly correlated with positive nasopharyngeal swabs (P = 0.028). The sampling lags from illness onset to sampling day in 3 out of 4 triple-positive patients and in 9 out of 10 dual-positive patients were respectively less than 9 days and less than 20 days. CONCLUSION: Our results indicate that the positive rate of SARS-CoV-2 on the ocular surface is much higher than expected. Transmission possibility through the ocular surface may be greatly underestimated.

Multiple cavernous hemangiomas in the orbit: A case report and review of the literature.

RATIONAL: Cavernous hemangiomas are one of the most common benign primary orbital lesions. These tumors are insidious in onset, slowly progressive and present more often in middle aged women. Multiple orbital cavernous hemangiomas are extremely rare, and only a few cases have been reported in the published literature. PATIENT CONCERNS: Here, we report the diagnosis and treatment of multiple cavernous hemangiomas in the right orbit of a female patient with impaired visual acuity and proptosis of the eye for more than 10 years. DIAGNOSIS: Magnetic resonance imaging of the orbit showed a giant and irregular soft mass filling the intraconal and extraconal space of the right orbit, compressing the right optic nerve. After tumor resection, histopathological examination confirmed the diagnosis of cavernous hemangioma. INTERVENTIONS: A lateral orbitotomy was performed and a total of 13 tumors were excised, with the largest tumor measuring approximately 2.5 × 3.0 cm. OUTCOMES: The visual acuity of the patient was preserved, with only a slightly dilated pupil of the right eye. The follow-up period was 6 months with no signs of recurrence. LESSONS: Multiple cavernous hemangiomas in the orbit is rare and should be excised surgically as soon as possible.

Integrative analysis of an lncRNA­associated competing endogenous RNA network in human trabecular meshwork cells under oxidative stress.

Long non­coding RNAs (lncRNAs) are a group of non­coding transcripts of >200 nucleotides. They can act as competing endogenous RNAs (ceRNAs) and suppress microRNA (miRNA) function by preventing them from binding to and interacting with target mRNAs. However, the specific role of the lncRNA­associated ceRNA network in the pathogenesis of glaucoma has not yet been elucidated. To study this, data were downloaded from the Gene Expression Omnibus database (GSE126170), which contained three human trabecular meshwork cell (HTMC) samples treated with 300 µm hydrogen peroxide and three control samples treated with vehicle. Differentially expressed lncRNAs and mRNAs of HTMCs were obtained using the R package limma. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of differentially expressed mRNAs were performed using the R package clusterProfiler. Finally, the ceRNA network was constructed using the mircode, miRDB, miRTarBase and TargetScan databases, and visualized using Cytoscape v3.6.1. The results showed that 70 lncRNAs and 558 mRNAs were identified to be significantly dysregulated (|log2FoldChange| >1 and adjusted P<0.05) in HTMCs under oxidative stress compared to those in HTMCs under control conditions. Moreover, 24 lncRNAs, 24 miRNAs and 40 mRNAs were closely connected, and were part of the ceRNA network. Among these, the expression levels of 19 lncRNAs were upregulated, and those of 5 lncRNAs were downregulated. To conclude, using bioinformatics analysis, the differential expression profiles of lncRNAs were reported and a lncRNA­associated ceRNA network in HTMCs under oxidative stress was constructed. These results may bring to light a new pathological mechanism or a potential therapeutic target for glaucoma.

The Effect of Dietary Vitamin K1 Supplementation on Trabecular Meshwork and Retina in a Chronic Ocular Hypertensive Rat Model.

Purpose: The pathophysiologic relationship between vitamin K and glaucoma remains largely unknown. The aim of the study was to explore the effect of dietary vitamin K supplementation in a rat glaucoma model. Methods: Rats were randomly divided into two groups: standard diet and high vitamin K1 (VitK1) diet (300 mg VitK1/kg diet). Induction of chronic ocular hypertension by episcleral vein cauterization was performed on the right eye. The left eye with sham operation served as controls. Rats received standard or high VitK1 diets for 5 weeks after surgery until the end of experiment. Immunohistochemistry analyses of the retina and trabecular meshwork were performed. The change in coagulation function and IOP were evaluated. Results: We observed a significant declined IOP at 2 weeks after surgery in the high VitK1 group compared with the control group. High VitK1 showed no significant effect on the body weight, rat phenotypes, or coagulation function. High VitK1 significantly inhibited the loss of retinal ganglion cells in the retina and increased the expression of matrix gla protein. High VitK1 also ameliorated the collapsed trabecular meshwork structure and increased collagen staining in the trabecular meshwork. Conclusions: High VitK1 intake inhibited the loss of retinal ganglion cells during glaucomatous injury, probably by increasing the expression of matrix gla protein. A transient decrease in the IOP was observed in the high VitK1 group, implying a potential effect of VitK1 on aqueous outflow. Retinal ganglion cells protection by high VitK1 supplementation may be due to the IOP-lowering effects as well as neuroprotective effect. Further research is required to delineate these processes.