Causal relationship between central corneal thickness and open-angle glaucoma: Evidence from Mendelian randomization.

Glaucoma is the leading cause of irreversible blindness worldwide. Previous observational studies have suggested a relationship between central corneal thickness (CCT) and glaucoma; however, the results are inconsistent. This study aimed to investigate whether CCT is associated with a risk for developing open-angle glaucoma (OAG). We employed two-sample Mendelian randomization to assess the relationship between CCT and OAG, namely, primary open-angle glaucoma (POAG) and suspected glaucoma. Genetic instruments composed of variants associated with CCT at genome-wide significance (P < 5 × 10-8) were obtained from published genome-wide association studies from Iglesias et al. for discovery and Bonnemaijer et al. for replication. Summary-level statistics for these instruments for the OAG were obtained from the FinnGen Project (Release 10). Inverse-variance-weighted regression of genetic susceptibility predicted that increased CCT was positively associated with an increased risk for POAG (odds ratio [OR], 1.005; 95% confidence interval [CI], 1.002-1.008; P = 0.001) and suspected glaucoma (OR, 1.006; 95% CI, 1.003-1.009; P < 0.001). In the replication sample of CCT, increased CCT was also positively associated with an increased risk for POAG (OR, 1.004; 95% CI, 1.000-1.008; P = 0.029) and suspected glaucoma (OR, 1.005; 95% CI, 1.001-1.008; P = 0.013). We found genetic evidence supporting a potential causal association between increased CCT and the risk of POAG and suspected glaucoma in the European population. This findings indicates the clinical significance of CCT in the diagnosis and treatment of glaucoma. Further studies are needed to elucidate the underlying mechanisms of this causal relationship.

Occlusion Robust Cognitive Engagement Detection in Real-World Classroom.

Cognitive engagement involves mental and physical involvement, with observable behaviors as indicators. Automatically measuring cognitive engagement can offer valuable insights for instructors. However, object occlusion, inter-class similarity, and intra-class variance make designing an effective detection method challenging. To deal with these problems, we propose the Object-Enhanced-You Only Look Once version 8 nano (OE-YOLOv8n) model. This model employs the YOLOv8n framework with an improved Inner Minimum Point Distance Intersection over Union (IMPDIoU) Loss to detect cognitive engagement. To evaluate the proposed methodology, we construct a real-world Students' Cognitive Engagement (SCE) dataset. Extensive experiments on the self-built dataset show the superior performance of the proposed model, which improves the detection performance of the five distinct classes with a precision of 92.5%.

Sympathetic Activation Promotes Cardiomyocyte Apoptosis in a Rabbit Susceptibility Model of Hyperthyroidism-Induced Atrial Fibrillation via the p38 MAPK Signaling Pathway.

Excess thyroid hormone secretion can cause endocrine metabolic disorders, which can lead to cardiovascular diseases, including heart enlargement, atrial fibrillation (AF), and heart failure. The present study investigated the molecular mechanisms of hyperthyroidism-induced AF. A rabbit susceptibility model of hyperthyroidism-induced AF was constructed, and metoprolol treatment was administered. Norepinephrine levels were determined using enzyme-linked immunosorbent assay; quantitative reverse transcription polymerase chain reaction and immunohistochemistry were used to detect the expression of markers for sympathetic remodeling (growth associated protein 43 and tyrosine hydroxylase in atrial myocardial tissues and stellate ganglia). Primary rabbit cardiomyocytes were cultured and identified by immunofluorescence staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining was used to measure cardiomyocyte apoptosis; western blot was used to detect the expression of apoptosis-related proteins, including Bax, Bcl-2, and cleaved caspase-3, as well as to measure the phosphorylation states of p38 mitogen-activated protein kinase (MAPK) pathway proteins. Metoprolol inhibited sympathetic activation and cardiomyocyte apoptosis in the rabbit model by inhibiting the p38 MAPK signaling pathway. Immunofluorescence staining results revealed that the rabbit cardiomyocytes were isolated successfully. Inhibition of p38 MAPK signaling alleviated norepinephrine-induced apoptosis in cardiomyocytes. Sympathetic activation promotes apoptosis in cardiomyocytes with hyperthyroidism-induced AF via the p38 MAPK signaling pathway. The results of the present study provide a novel theoretical basis for the potential clinical treatment of patients with hyperthyroidism and AF.

Small peptide LINC00511-133aa encoded by LINC00511 regulates breast cancer cell invasion and stemness through the Wnt/ß-catenin pathway.

LINC00511 is an long non-coding RNA (lncRNA) of ncRNAs,This study aimed to investigate whether the lncRNA LINC00511 could encode a small peptide, LINC00511-133aa, and whether this peptide could promote breast cancer cell metastasis and stemness by activating the wnt/ß-catenin pathway. The LINC00511-133aa coding sequence vector and control vector were transfected into MCF-7 and MDA-MB-231 breast cancer cells, with subsequent assessment of peptide expression using PCR, western blotting, and immunofluorescence assays. Cell proliferation, invasion, and apoptosis were evaluated using CCK8, apoptotic, wound healing, and transwell invasion assays, while the characteristic changes of tumor stem cells were detected through sphere-forming assay and western blot analyses of the stemness markers Oct4, Nanog, and SOX2. Results showed that LINC00511-133aa was indeed encoded by LINC00511 and promoted the invasiveness and stemness of breast cancer cells while limiting apoptosis by modulating the expression levels of wnt/ß-catenin pathway-related proteins Bax, c-myc, and CyclinD1, as well as facilitating ß-catenin protein entry into the nucleus. This study provides evidence for the potential involvement of lncRNA LINC00511 and its peptide product in breast cancer progression via the regulation of the wnt/ß-catenin pathway.

Bimodal Learning Engagement Recognition from Videos in the Classroom.

Engagement plays an essential role in the learning process. Recognition of learning engagement in the classroom helps us understand the student's learning state and optimize the teaching and study processes. Traditional recognition methods such as self-report and teacher observation are time-consuming and obtrusive to satisfy the needs of large-scale classrooms. With the development of big data analysis and artificial intelligence, applying intelligent methods such as deep learning to recognize learning engagement has become the research hotspot in education. In this paper, based on non-invasive classroom videos, first, a multi-cues classroom learning engagement database was constructed. Then, we introduced the power IoU loss function to You Only Look Once version 5 (YOLOv5) to detect the students and obtained a precision of 95.4%. Finally, we designed a bimodal learning engagement recognition method based on ResNet50 and CoAtNet. Our proposed bimodal learning engagement method obtained an accuracy of 93.94% using the KNN classifier. The experimental results confirmed that the proposed method outperforms most state-of-the-art techniques.

Pars plana subcapsulotomy to remove condense subcapsular opacification in combined surgery of silicone oil removal and phacoemulsification.

PURPOSE: Because of the direct contact of intravitreal silicone oil (SO) with the subcapsular membrane, cataract is one of the main SO-related complications. In a group of patients, condense subcapsular opacification occurs, which adds difficulty and risk when having sequential treatment of it. The aim of the current study is to assess the long-term outcomes of pars plana subcapsulotomy to remove condense subcapsular opacification in combined surgery of SO removal and phacoemulsification. METHODS: Retrospective cohort study. Consecutive patients who were scheduled to have combined surgery of SO removal and phacoemulsification, and with condense subcapsular opacification were included. After phacoemulsification and SO removal, circular subcapsulotomy (diameter = 3-5 mm) was performed with a 23-/25-gauge vitrectomy probe on each subject during the combined surgery. Main outcomes were pre- and postoperative best-corrected visual acuity (BCVA), intra- and postoperative complications. RESULTS: One hundred and twenty patients (120 eyes) were included. Postoperative logMAR BCVA at day 1, week 1, month 1, and final follow-up examinations was 1.0 ± 0.5, 0.7 ± 0.4, 0.6 ± 0.4, and 0.6 ± 0.3, respectively. Statistically significant median differences of logMAR BCVA occurred between the preoperative examination and each postoperative follow-up examination (all p < 0.001). The sharpest median increase in logMAR BCVA occurred between the day 1 and week 1 postoperative examinations (p < 0.001). CONCLUSIONS: For condense subcapsular opacification caused by SO tamponade, pars plana subcapsulotomy with a 23-/25-gauge vitrectomy probe during combined surgery of SO removal and phacoemulsification is effective and safe to have surgical management of it. The systemic approach enables patients to experience rapid and long-lasting vision rehabilitation in a single procedure.

Combined 23-G Pars Plana Vitrectomy and Lensectomy in the Management of Glaucoma Associated with Nanophthalmos.

PURPOSE: To investigate the surgical results of 23-G pars plana vitrectomy (PPV) combined with lensectomy (PPL) in nanophthalmic patients with angle closure glaucoma. METHODS: This prospective nonrandomized study included consecutive patients with nanophthalmic glaucoma recruited for 23-G PPV combined with PPL. Best-corrected visual acuity (BCVA), intraocular pressure (IOP), the number of antiglaucoma medications, and surgery-associated complications were recorded. Surgical success rates were evaluated at each follow-up. Prognostic factors for success were also assessed using logistic regression analysis. RESULTS: This study enrolled 21 eyes of 21 patients. The mean follow-up was 18.6 ± 7.0 months. At the final follow-up visit, the mean IOP was significantly reduced (from 47.4 ± 5.7 to 18.6 ± 3.6 mm Hg). The mean number of antiglaucoma medications dropped from 5 to 0. BCVA improved in 3 (14.3%) eyes. The complete success rate (IOP >6 and <21 mm Hg without antiglaucoma medication) was 71.4, 66.7, and 71.4% at the 6-month, 12-month, and final follow-up visit, respectively. CONCLUSIONS: Nanophthalmic glaucoma can be effectively managed with the combined surgery of 23-G PPV and PPL. IOP control was achieved with elimination of pupillary block and deepening of the anterior chamber. This surgical procedure proved to be safe in eyes with a potential risk of vision-threatening complications.

Altered Macular Microvasculature in Mild Cognitive Impairment and Alzheimer Disease.

BACKGROUND: The goal of the present study was to analyze the macular microvacular network in mild cognitive impirment (MCI) and Alzheimer disease (AD). METHODS: Twelve patients with AD and 19 patients with MCI were recruited together with 21 cognitively normal controls with a similar range of ages. Optical coherence tomography angiography was used to image the retinal microvascular network at the macular region, including retinal vascular network (RVN), superficial vascular plexus (SVP), and deep vascular plexus (DVP). Fractal analysis (box counting, Dbox) representing the microvascular density was performed in different annular zones and quadrantal sectors. The macular ganglion cell-inner plexiform layer (GC-IPL) thickness was measured using Zeiss OCT. The relationship between the retinal microvasculature and clinical manifestations was analyzed. RESULTS: Patients with AD had lower densities of RVN, SVP, and DVP in the annulus, from 0.6 to 2.5 mm in diameter (P < 0.05) in comparison with controls. Patients with MCI had lower density of DVP in the superior nasal quadrant (P < 0.05) than that of the controls. There were no significant differences of GC-IPL thickness among groups (P > 0.05). There was a trend of vascular density loss from control to MCI then AD (P < 0.05). Retinal microvascular density of DVP was correlated with GC-IPL thickness (P < 0.05) in patients with AD, but not in patients with MCI and controls. CONCLUSIONS: Patients with AD had less density of retinal microvascular networks than controls. Our findings suggest the presence of retinal microvascular dysfunction in AD.

Surgical outcomes of 27-gauge pars plana vitrectomy with short-term postoperative tamponade of perfluorocarbon liquid for repair of giant retinal tears.

PURPOSE: To investigate the use of 27-gauge pars plana vitrectomy (PPV) with short-term tamponade of perfluorocarbon liquid (PFCL) for repair of giant retinal tears (GRT). METHODS: Retrospective case series study. Consecutive patients with GRT were treated with 27-gauge PPV and short-term tamponade of PFCL for 7-10 days. PFCL was completely removed with a secondary surgery. RESULTS: Twenty-three eyes of 23 patients were included. All the patients achieved primary anatomic success. Preoperative logarithm of the minimum angle of resolution (logMAR) BCVA was 1.59 ± 0.58 (Snellen 20/778). Five (21.7%), nine (39.1%), eleven (47.8%) and fifteen (65.2%) eyes experienced vision improvement at the Month-1, Month-3, Month-6 and final follow-ups, respectively. The final logMAR BCVA was 0.84 ± 0.51 (Snellen 20/138), being statistically better than the preoperative one (P < 0.001). Surgical complications included foreign body response (n = 7), transient elevated intraocular pressure (n = 5), cataract formation/deterioration (n = 11) and posterior capsule opacity (n = 16). CONCLUSIONS: 27-Gauge PPV with short-term tamponade of PFCL is safe and effective for the repair of GRT. Side effects of the surgery mainly included foreign body response, transient elevated intraocular pressure, cataract formation/deterioration and posterior capsule opacity.

PARS PLANA VITRECTOMY AND WIDE INTERNAL LIMITING MEMBRANE PEELING WITH PERFLUOROPROPANE TAMPONADE FOR HIGHLY MYOPIC FOVEOSCHISIS-ASSOCIATED MACULAR HOLE.

PURPOSE: To evaluate the outcomes of pars plana vitrectomy and wide internal limiting membrane peeling with perfluoropropane tamponade (C3F8) for highly myopic foveoschisis-associated macular hole. METHODS: Prospective consecutive cases with highly myopic foveoschisis-associated macular hole were recruited. All the patients underwent pars plana vitrectomy and indocyanine green-aided internal limiting membrane peeling, the range of internal limiting membrane peeling was broadened beyond the vascular arcades and to the nasal side of the optic disc. With tamponade of 16% C3F8, all the patients kept a face-down position postoperatively. The main outcomes were best-corrected visual acuity and primary anatomical success rate. RESULTS: There were 25 patients (25 eyes) included, with a mean age of 54.8 ± 7.2 years. The mean follow-up duration was 14.2 ± 3.9 months. The mean preoperative logarithm of the minimum angle of resolution best-corrected visual acuity (Snellen equivalent) was 1.489 ± 0.558 (20/617). The mean postoperative logarithm of the minimum angle of resolution best-corrected visual acuity at the final follow-up was 0.882 ± 0.522 (20/152), the difference being statistically significant with the preoperative one (P < 0.001). At the final follow-up, 17 eyes (68.0%) had vision improvement, and the primary anatomical success rate was 84.0% (21/25). CONCLUSION: Pars plana vitrectomy and wide internal limiting membrane peeling with C3F8 tamponade is effective and safe to achieve a high anatomical success rate of highly myopic foveoschisis-associated macular hole closure and regain visual function.

Pars plana vitrectomy with partial tamponade of filtered air in Rhegmatogenous retinal detachment caused by superior retinal breaks.

BACKGROUND: To investigate the anatomic and functional outcomes of pars plana vitrectomy (PPV) with partial tamponade of filtered air for rhegmatogenous retinal detachment (RRD) caused by superior retinal breaks. METHODS: Retrospective, comparative, consecutive case series study. Patients with RRD caused by superior retinal breaks undergone PPV with partial tamponade (Group A) and whole tamponade (Group B) of filtered air were included. The main outcomes were primary and final success rates, best corrected visual acuity (BCVA), and rate of postoperative cataract surgery. RESULTS: Forty-one patients (41 eyes) were included in Group A and 36 patients (36 eyes) were included in Group B. There were no significant differences in primary or final success rates between Groups A and B (P = 0.618 and P = 1.000, respectively). The patients in Group A experienced quicker postoperative vision improvement (from the Week 1 follow-up) than the patients in Group B (from the Month 3 follow-up). The postoperative cataract surgery rate of Group A (7/31) was lower than that of Group B (13/26) (P = 0.031). CONCLUSIONS: PPV with partial tamponade of air is effective in achieving a high anatomic success rate, quicker postoperative vision improvement, and lower rate of postoperative cataract surgery in RRD caused by superior retinal breaks.

Mutation survey and genotype-phenotype analysis of COL2A1 and COL11A1 genes in 16 Chinese patients with Stickler syndrome.

PURPOSE: To identify mutations in COL2A1 and COL11A1 genes and to examine the genotype-phenotype correlation in a cohort of Chinese patients with Stickler syndrome. METHODS: A total of 16 Chinese probands with Stickler syndrome were recruited, including nine with a family history of an autosomal dominant pattern and seven sporadic cases. All patients underwent full ocular and systemic examinations. Sanger sequencing was used to analyze all coding and adjacent regions of the COL2A1 and COL11A1 genes. Multiplex ligation-dependent probe amplification was performed to detect the gross indels of COL2A1 and COL11A1. Bioinformatics analysis was performed to evaluate the pathogenicity of the variants. RESULTS: Five mutations in COL2A1 were identified in six of 16 probands, including three novel (c.85C>T, c.3356delG, c.3401delG) mutations and two known mutations (c.1693C>T, c.2710C>T). Of the five mutations, three were truncated mutations, and the other two were missense mutations. Putative pathogenic mutations of the COL11A1 gene were absent in this cohort of patients. Gross indels were not found in COL2A1 or COL11A1 in any of the probands. High myopia was the most frequent initial ocular phenotype of Stickler syndrome. In this study, 12 Chinese probands lacked obvious systemic phenotypes. CONCLUSIONS: In this study, three novel and two known mutations in the COL2A1 gene were identified in six of 16 Chinese patients with Stickler syndrome. This is the first study in a cohort of Chinese patients with Stickler syndrome, and the results expand the mutation spectrum of the COL2A1 gene. Analysis of the genotype-phenotype correlation showed that the early onset of high myopia with vitreous abnormalities may serve as a key indicator of Stickler syndrome, while the existence of mandibular protrusion in pediatric patients may be an efficient indicator for the absence of mutations in COL2A1 and COL11A1.

Surgical outcomes of 23-gauge transconjunctival pars plana vitrectomy combined with lensectomy for glaucomatous eyes with extremely shallow anterior chamber and cataract.

BACKGROUND: Glaucoma combined with an extremely shallow anterior chamber and cataracts remains as a complex condition to deal with. And the emergence of microincision vitrectomy surgery (MIVS) system may provide an ideal option for the treatment of that. We report a clinical study of surgical outcomes of 23-gauge transconjunctival pars plana vitrectomy (PPV) combined with lensectomy in the treatment of glaucomatous eyes with extremely shallow anterior chamber and cataract. METHODS: Prospective, nonrandomized and noncomparative case series study. Consecutive patients with secondary glaucoma, extremely shallow anterior chamber and cataract were recruited to have combined surgeries of 23-gauge transconjunctival pars plana vitrectomy and lensectomy. The main outcomes were best corrected visual acuity (BCVA), intraocular pressure (IOP), anterior chamber depth (ACD), number of anti-glaucoma medications and surgery-associated complications. RESULTS: Seventeen consecutive patients with secondary glaucoma, extremely shallow anterior chamber and cataract were recruited. The mean follow-up was 21.2 ± 8.8 months. Postoperatively, there was no significant improvement of BCVA (P = 0.25). The mean intraocular (IOP) decreased significantly from 43.14 ± 6.53 mmHg to 17.29 ± 1.80 mmHg (P < 0.001), and the mean depth of anterior chamber increased significantly from 0.507 ± 0.212 mm to 3.080 ± 0.313 mm (P < 0.001). The mean number of anti-glaucoma medications decreased from 4.1 ± 0.8 to 0.6 ± 0.8 (P < 0.001). No severe vision-threatening intra- or post-operative complications occurred. CONCLUSIONS: Glaucoma with an extremely shallow anterior chamber and cataract can be managed well with the combined surgeries of 23-gauge pars plana vitrectomy and lensectomy. The surgical procedure is an effective and safe method to resolve the pupillary block and deepen the anterior chamber.

A SURGICAL APPROACH TO LARGE SUBRETINAL HEMORRHAGE USING PARS PLANA VITRECTOMY AND 360° RETINOTOMY.

PURPOSE: To evaluate the surgical approach of pars plana vitrectomy combined with 360° retinotomy and silicon oil tamponade in the treatment of patients with large subretinal hemorrhage. METHODS: Prospective, nonrandomized, and noncomparative case series study. Consecutive patients with breakthrough vitreous hemorrhage and massive subretinal hemorrahge were recruited to have combined surgery of pars plana vitrectomy with 360° retinotomy and silicone oil temponade. The main outcomes were best-corrected visual acuity, retina status, and postoperative complications. RESULTS: Twenty-one patients (21 eyes) were included. The mean follow-up was 19.9 ± 7.4 months. The mean preoperative thickness of subretinal hemorrhage was 4.25 ± 0.69 mm. All the patients were observed to have choroidal neovascularization during the surgical procedure. The mean logarithm of the minimum angle of resolution best-corrected visual acuity (Snellen equivalent) significantly improved from preoperatively 2.64 (hand movement) to 1.73 (7/400), 1.50 (6/200), 1.51 (6/200), and 1.45 (7/200) at 1 month, 3 months, 6 months after the initial surgery, and final follow-up. Postoperative complications included temporary higher intraocular pressure, silicone oil emulsification, lens opacification, epimacular membrane, retinal pigment epithelium loss, and subretinal fibrosis. At the end of the follow-up, retinas were all reattached without any recurrence of choroidal neovascularization. CONCLUSION: Pars plana vitrectomy combined with retinotomy and silicone oil tamponade is effective for eyes with breakthrough vitreous hemorrhage and massive subretinal hemorrahge.

A machine-independent method to have active removal of 5,000 centistokes silicone oil using plastic infusion tube and 23-gauge microcannulas.

BACKGROUND: To describe one modified method of having machine-independent removal of 5,000 centistokes silicone oil through 23-gauge trocar-cannulas. METHODS: Consecutive patients with silicone oil tamponade for more than four months and with complete retinal reattachment were included. Two 23-gauge trocars were used to make sclerotomies while the microcannulas remained in situ for intravitreous infusion and silicone oil drainage. A short section of infusion tube was connected with a 10 ml syringe's needle adapter. The other side was attached to the conjunctiva surface and covered the cannula's cap inside to form a closed space for silicone oil drainage. The main outcomes were duration for complete removal of silicone oil and intra- and postoperative complications. RESULT: There were totally twenty cases (20 eyes) included. The mean time for draining out the silicone oil was 4.54 ± 0.78 minutes. Intraoperatively, flute needle was introduced additionally in seven cases to achieve complete removal. No cases experienced postoperative visual acuity deterioration or refractory hypotony. No significant residual oil bubbles were observed. No retinal redetachment occurred throughout the follow-ups. CONCLUSION: The modified method of using an infusion tube and 23-gauge trocar-cannulas can achieve quick and complete removal of high viscosity silicone oil.

Modified technique for transscleral fixation of posterior chamber intraocular lenses.

BACKGROUND: Suture exposure remains to be a potential problem of transscleral fixated posterior chamber intraocular lens (PCIOL). We report a modified technique to minimize the risk of suture exposure for the transscleral fixation of PCIOL. METHODS: The modified surgical technique is as following: at first, two 3 mm × 4 mm square scleral pockets were created from groove incisions at opposite positions. A straight needle attached to a 10-0 polypropylene suture was passed through one incision groove. Then, a 27-Gauge hollow needle passed through the opposite sclera incision bed was used to retrieve the straight fine needle via its barrel. The sutures were tied to themselves after one more bite on the scleral bed. At last, the suture ends were left long (about 4 mm) and laid flat into corresponding laminar scleral pockets. This modified technique of PCIOL was performed in 48 post-traumatic aphakic vitrectomized eyes from 48 patients (47 male, one female) with mean age of 34.8 ± 14.8 years. Main outcome measures included best corrective visual acuity (BCVA), IOL decentration, IOL tilt, and postoperative complications. RESULTS: The mean follow-up was 32.3 ± 10.8 months (3-67 months). The LogMAR BCVA remained stable, from a preoperative value of 0.46 ± 0.34 to postoperative 0.44 ± 0.34 (p = 0.69). Mild IOL tilt (5-10°) was observed in five eyes, and slight IOL decentration (0.5-1.0 mm) was seen in three cases. No case of suture exposure, suture breakage, IOL dislocation, or endophthalmitis was observed during the follow up period. CONCLUSION: The modified technique allowed stable placement of PCIOLs in post-traumatic aphakic eyes with a wide range of follow-up. Our procedure might have the potential benefit to avoid suture exposure in scleral-fixated IOL implantation.

Setanaxib mitigates oxidative damage following retinal ischemia-reperfusion via NOX1 and NOX4 inhibition in retinal ganglion cells.

Glaucoma, a prevalent cause of permanent visual impairment worldwide, is characterized by the progressive degeneration of retinal ganglion cells (RGCs). NADPH oxidase (NOX) 1 and NOX4 are pivotal nodes in various retinal diseases. Setanaxib, a potent and highly selective inhibitor of NOX1 and NOX4, can impede the progression of various diseases. This study investigated the efficacy of setanaxib in ameliorating retinal ischemia-reperfusion (I/R) injury and elucidated its underlying mechanisms. The model of retinal I/R induced by acute intraocular hypertension and the oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary RGCs were established. By suppressing NOX1 and NOX4 expression in RGCs, setanaxib mitigated I/R-induced retinal neuronal loss, structural disruption, and dysfunction. Setanaxib reduced TUNEL-positive cells, upregulated Bcl-2, and inhibited Bax, Bad, and cleaved-caspase-3 overexpression after I/R injury in vitro and in vivo. Moreover, setanaxib also significantly reduced cellular senescence, as demonstrated by downregulating SA-ß-gal-positive and p16-INK4a expression. Furthermore, setanaxib significantly suppressed ROS production, Hif-1α and FOXO1 upregulation, and NRF2 downregulation in damaged RGCs. These findings highlight that the setanaxib effectively inhibited NOX1 and NOX4, thereby regulating ROS production and redox signal activation. This inhibition further prevents the activation of apoptosis and senescence related factors in RGCs, ultimately protecting them against retinal I/R injury. Consequently, setanaxib exhibits promising potential as a therapeutic intervention for glaucoma.

BMX deletion mitigates neuroinflammation induced by retinal ischemia/reperfusion through modulation of the AKT/ERK/STAT3 signaling cascade.

Aims: Retinal ischemia/reperfusion (I/R) injury is implicated in the etiology of various ocular disorders. Prior research has demonstrated that bone marrow tyrosine kinase on chromosome X (BMX) contributes to the advancement of ischemic disease and inflammatory reactions. Consequently, the current investigation aims to evaluate BMX's impact on retinal I/R injury and clarify its implied mechanism of action. Main methods: This study utilized male and female systemic BMX knockout (BMX-/-) mice to conduct experiments. The utilization of Western blot assay and immunofluorescence labeling techniques was employed to investigate variations in the expression of protein and tissue localization. Histomorphological changes were observed through H&E staining and SD-OCT examination. Visual function changes were assessed through electrophysiological experiments. Furthermore, apoptosis in the retina was identified using the TUNEL assay, as well as the ELISA technique, which has been utilized to determine the inflammatory factors level. Key findings: Our investigation results revealed that the knockdown of BMX did not yield a significant effect on mouse retina. In mice, BMX knockdown mitigated the negative impact of I/R injury on retinal tissue structure and visual function. BMX knockdown effectively reduced apoptosis, suppressed inflammatory responses, and decreased inflammatory factors subsequent to I/R injury. The outcomes of the current investigation revealed that BMX knockdown partially protected the retina through downregulating phosphorylation of AKT/ERK/STAT3 pathway. Significance: Our investigation showed that BMX-/- reduces AKT, ERK, and STAT3 phosphorylation, reducing apoptosis and inflammation. Thus, this strategy protected the retina from structural and functional damage after I/R injury.

Rac1 modulates the vitreous-induced plasticity of mesenchymal movement in retinal pigment epithelial cells.

BACKGROUND: The vitreous has been shown to induce epithelial-mesenchymal transdifferentiation because it induces fibroblast-like morphology, enhanced migration and invasion in retinal pigment epithelial cells in proliferative vitreoretinopathy. Rac1 is the principal mediator of cell migration. In the current study, the relationship between Rac1 and cell migration, and invasion in vitreous-transformed retinal pigment epithelial cells was investigated using NSC23766, a specific inhibitor of Rac guanosine-5'-triphosphatase activity, and the involvement of a Rac1 guanosine-5'-triphosphatase-dependent pathway was detected. DESIGN: One-way design with multiple levels and repeated measurement design. PARTICIPANTS AND SAMPLES: The vitreous humor was collected from 20 healthy donor eyes and the retinal pigment epithelial cells were obtained from 9 healthy donor eyes. METHODS: Human low-passage retinal pigment epithelial cells were treated with normal medium or 25% vitreous medium. Rac1 activity was measured using a pull-down assay. The cytotoxicity of NSC23766 was measured using the trypan blue dye exclusion test. Cell migration was measured using a wound healing assay. Cell invasion was determined using a transwell invasion assay. Protein expression of Rac1 and phosphorylation of LIM kinase 1 and cofilin were detected by Western blot analysis. MAIN OUTCOME MEASURES: Cell migration, invasion, Rac1 activity and phosphorylation of LIM kinase 1 and cofilin. RESULTS: Rac1guanosine-5'-triphosphatase was activated in vitreous-transformed retinal pigment epithelial cells. A Rac inhibitor suppressed vitreous-induced migration and invasion in retinal pigment epithelial cells. Cofilin phosphorylation was activated by vitreous treatment but blocked by NSC23766. CONCLUSIONS: Rac1 mediates vitreous-transformed retinal pigment epithelial cells' plasticity of mesenchymal movement via Rac1 guanosine-5'-triphosphatase-dependent pathways that modulate LIM kinase 1 and cofilin activity. Rac inhibition may be considered a novel treatment for proliferative vitreoretinopathy.

MIR34A modulates lens epithelial cell apoptosis and cataract development via the HK1/caspase 3 signaling pathway.

Cataracts are the leading cause of blindness in the world. Age is a major risk factor for cataracts, and with increasing aging, the burden of cataracts will grow, but the exact details of cataractogenesis remain unclear. A recent study showed that microRNA-34a (MIR34A) is involved in the development of cataracts, but the underlying pathogenesis remains obscure. Here, our results of microRNA target prediction showed that hexokinase 1 (HK1) is one of the genes targeted by MIR34A. Based on this finding, we focused on the function of MIR34A and HK1 in the progress of cataracts, whereby the human lens epithelial cell line SRA01/04 and mouse lens were treated with MIR34A mimics and HK1 siRNA. We found that HK1 mRNA is a direct target of MIR34A, whereby the high expression of MIR34A in the cataract lens suppresses the expression of HK1. In vitro, the upregulation of MIR34A together with the downregulation of HK1 inhibits the proliferation, induces the apoptosis of SRA01/04 cells, and accelerates the opacification of mouse lenses via the HK1/caspase 3 signaling pathway. In summary, our study demonstrates that MIR34A modulates lens epithelial cell (LEC) apoptosis and cataract development through the HK1/caspase 3 signaling pathway.