Small extracellular vesicles derived from microRNA-22-3p-overexpressing mesenchymal stem cells protect retinal ganglion cells by regulating MAPK pathway.

Glaucoma is the leading cause of irreversible blindness and is characterized by progressive retinal ganglion cell (RGC) loss and retinal nerve fiber layer thinning. Currently, no existing treatment is effective for the preservation of RGCs. MicroRNA-22-3p (miR22) and small extracellular vesicles derived from mesenchymal stem cells (MSC-sEVs) have neuroprotective effects. In this study, we apply miR22-overexpressing MSC-sEVs in an N-methyl-D-aspartic acid (NMDA)-induced RGC injury model to assess their short-term therapeutic effects and explore the underlying mechanisms. We find that mice in the miR22-sEVs-treated group have thicker retinas, fewer apoptotic cells, more reserved RGCs, better retinal function, and lower expression levels of Bax and caspase-3. MiR22-sEVs treatment promotes viability, inhibits apoptosis and inhibits Bax and caspase-3 expression in RGC-5 cells. MiR22 targets mitogen-activated protein kinase kinase kinase 12 to inhibit apoptosis by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. Collectively, our results suggest that miR22-sEVs ameliorate NMDA-induced RGC injury through the inhibition of MAPK signaling pathway-mediated apoptosis, providing a potential therapy for glaucoma and other diseases that involve RGC damage.

Influence of reinforcement learning on the inhibitory control of Internet gaming disorder.

Reward processing dysfunction and inhibition control deficiency have been observed in Internet gaming disorder (IGD). However, it is still unclear whether the previous reinforcement learning depends on reward/punishment feedback influences on the cognitive inhibitory control of IGD. This study compared the differences between an IGD group and healthy people without game experiences in the probability selection task and the subsequent stop signal task by the method of behavioral experiments, in order to explore whether the reward learning ability is impaired in the IGD group. We also discuss the influence of previous reward learning on subsequent inhibition control. The results showed that (1) during the reward learning phase, the IGD group's accuracy was significantly lower than that of the control group; (2) compared with the control group, the IGD group's reaction times were longer in the transfer phase; (3) for no-go trials of the inhibitory control phase after reward learning, the accuracy of the reward-related stimulation in the IGD group was lower than that of punishment-related or neutral stimulation, but there was no significant difference among the three conditions in the control group. These findings indicated that the reinforcement learning ability of the IGD group was impaired, which further caused the abnormal response to reinforcement stimuli.

Modified technique for repositioning dislocated polymethylmethacrylate intraocular lenses with eyelets.

The aim of this study is to describe a modified technique for internal refixation of dislocated scleral-sutured polymethylmethacrylate (PMMA) intraocular lenses (IOLs) with eyelets. Three-port pars plana vitrectomy was performed. Through the scleral fixation site, a 30-gauge needle loaded with an 8-0 polypropylene suture was inserted into the vitreous cavity. The suture end was passed through the eyelet of IOL with 25-gauge forceps. Next, it was guided out of the eye through the original scleral fixation point. The end of the exterior suture was buried with a flapless intrascleral knotting technique. Six eyes of six patients were successfully treated with this technique and followed up for 6-12 months postsurgery. In all cases, there was significant improvement in uncorrected visual acuity. IOLs were stable with proper centration and no major complications. This modified technique offers an effective and minimally invasive surgical alternative for refixation of dislocated scleral-sutured PMMA IOLs with eyelets.

Neuroprotective effects of acteoside in a glaucoma mouse model by targeting Serta domain-containing protein 4.

AIM: To explore the therapeutic effect and main molecular mechanisms of acteoside in a glaucoma model in DBA/2J mice. METHODS: Proteomics was used to compare the differentially expressed proteins of C57 and DBA/2J mice. After acteoside administration in DBA/2J mice, anterior segment observation, intraocular pressure (IOP) monitoring, electrophysiology examination, and hematoxylin and eosin staining were used to analyze any potential effects. Immunohistochemistry (IHC) assays were used to verify the proteomics results. Furthermore, retinal ganglion cell 5 (RGC5) cell proliferation was assessed with cell counting kit-8 (CCK-8) assays. Serta domain-containing protein 4 (Sertad4) mRNA and protein expression levels were measured by qRT-PCR and Western blot analysis, respectively. RESULTS: Proteomics analysis suggested that Sertad4 was the most significantly differentially expressed protein. Compared with the saline group, the acteoside treatment group showed decreased IOP, improved N1-P1 wave amplitudes, thicker retina, and larger numbers of cells in the ganglion cell layer (GCL). The IHC results showed that Sertad4 expression levels in DBA/2J mice treated with acteoside were significantly lower than in the saline group. Acteoside treatment could improve RGC5 cell survival and reduce the Sertad4 mRNA and protein expression levels after glutamate injury. CONCLUSION: Sertad4 is differentially expressed in DBA/2J mice. Acteoside can protect RGCs from damage, possibly through the downregulation of Sertad4, and has a potential use in glaucoma treatment.

Metabolome profiling and transcriptome analysis filling the early crucial missing steps of piperine biosynthesis in Piper nigrum L.

Black pepper (Piper nigrum L.), the world renown as the King of Spices, is not only a flavorsome spice but also a traditional herb. Piperine, a species-specific piper amide, is responsible for the major bioactivity and pungent flavor of black pepper. However, several key steps for the biosynthesis of piperoyl-CoA (acyl-donor) and piperidine (acyl-acceptor), two direct precursors for piperine, remain unknown. In this study, we used guilt-by-association analysis of the combined metabolome and transcriptome, to identify two feruloyldiketide-CoA synthases responsible for the production of the C5 side chain scaffold feruloyldiketide-CoA intermediate, which is considered the first and important step to branch metabolic fluxes from phenylpropanoid pathway to piperine biosynthesis. In addition, we also identified the first two key enzymes for piperidine biosynthesis derived from lysine in P. nigrum, namely a lysine decarboxylase and a copper amine oxidase. These enzymes catalyze the production of cadaverine and 1-piperideine, the precursors of piperidine. In vivo and in vitro experiments verified the catalytic capability of them. In conclusion, our findings revealed enigmatic key steps of piperine biosynthetic pathway and thus provide a powerful reference for dissecting the biosynthetic logic of other piper amides.

Restoration of vision in Kniest dysplasia patient characterized by retinal detachment with dialysis of the ora serrata: A case report.

INTRODUCTION: Congenital eye diseases have a significant impact on children and young adults. Retinal detachment associated with Kniest dysplasia represents the most severe ocular complication, which is challenging to diagnose and treat effectively. Genetic testing has emerged as an invaluable tool for diagnosing hereditary diseases. CASE PRESENTATION: A 23-year-old male presented to our Ophthalmology Clinic with retinal detachment involving dialysis of the ora serrata in his left eye. High-throughput exon sequencing enabled a definitive diagnosis of Kniest dysplasia resulting from a mutation in the COL2A1 gene. The patient subsequently underwent pars plana vitrectomy with silicone oil injection to reattach the retina. This surgical intervention successfully reattached the retina and restored vision to 20/25 in the affected eye. CONCLUSION: Retinal detachment represents the most serious ocular complication associated with Kniest dysplasia. To prevent permanent blindness, early diagnosis through genetic testing and regular ophthalmological examinations are imperative. Advances in genetic screening have improved the management of retinal detachment risk in Kniest dysplasia patients.

China Glaucoma Treatment Pattern Study I-Primary Angle-Closure Glaucoma: protocol for a multicentre, retrospective, observational study.

INTRODUCTION: Primary angle-closure glaucoma (PACG) is a leading cause of irreversible blindness globally, and the number of patients with PACG rises every year. Yet, there is a lack of knowledge about the clinical characteristics, therapeutic options and profile of patients with PACG in China. Hence, we design the China Glaucoma Treatment Pattern Study Ⅰ-Primary Angle-Closure Glaucoma (Ch-GTPⅠ). The objective of this paper is to describe the design and methodology of Ch-GTP. The aim of this study is to characterise the profile and trend associated with initial PACG treatment for the last 10 years in China. METHODS: Ch-GTPⅠ is a national multicentre retrospective observational study that will randomly sample from 50 hospitals throughout China. Over 7000 patient records hospitalised for initial PACG treatment from 2011 to 2020 will be selected randomly. The data from electronic medical records will be uploaded to an encrypted online platform that will receive and collate data from all collaborating hospitals. Data abstraction and monitoring will be performed in a standardised manner by trained statisticians to ensure consistency. Systematic data cleaning will also be conducted by statisticians to ensure data integrity before final data storage. The outcomes will include four broad categories: (1) demographics, (2) clinical characteristics, (3) therapeutic strategies and procedures and (4) early outcomes at discharge. The demographic characteristics and early outcomes will be summarised using descriptive statistics. Comparative analyses of characteristics and treatment pattern changing trends for different regions and years will be used to test for significant differences (t-test or Mann-Whitney U test). ETHICS AND DISSEMINATION: The collaborating hospitals obtained local approval based on a standard ethics application from internal ethics committees or acknowledged an existent ethics approval of the leading institution with approval from internal ethics committees. Due to the retrospective nature, written informed consent from patients was waived by the ethics committee. The results will be published in academic journals and presented at national and international academic conferences. TRIAL REGISTRATION NUMBER: ChiCTR2100054643.

Thinning of the Lamina Cribrosa and Deep Layer Microvascular Dropout in Patients With Open Angle Glaucoma and High Myopia.

PRCIS: Lamina cribrosa (LC) thinning (thickness of ≤128.00 µm) helps to distinguish open angle glaucoma from high myopia, which was associated with the presence of microvasculature dropout and elevated intraocular pressure. PURPOSE: The purpose of this study was to analyze the factors associated with LC thickness in highly myopic eyes with and without open angle glaucoma. METHODS: In total, 240 highly myopic eyes with γ-zones (194 eyes without and 46 eyes with open angle glaucoma) were examined, and the LC center, externally oblique border, an abrupt change of scleral curvature (scleral step), deep layer microvasculature dropout and global retinal nerve fiber layer thickness were investigated on optical coherence tomography and optical coherence tomography angiography. RESULTS: LC were thinner in highly myopic open angle glaucoma compared with high myopia alone (107.76±9.86 vs. 137.07±18.51 µm, P <0.001), which was associated with deep layer microvasculature dropout and elevated intraocular pressure. The areas under the receiver operating characteristic curve for detecting open angle glaucoma from the LC thickness was 0.964, which was statistically higher ( P <0.05) than from the global retinal nerve fiber layer thickness (0.921) and vertical cup-to-disc ratio (0.902). A LC thickness cutoff value of 128 µm provided 100% sensitivity for detecting open angle glaucoma with 84% specificity. CONCLUSIONS: Highly myopic eyes with open angle glaucoma appear to have a thinner LC, which was associated with elevated intraocular pressure and deep layer microvasculature dropout. LC thinning (≤128.00 µm) helps distinguish open angle glaucoma from high myopia with an abnormal retinal nerve fiber layer thickness distribution and unclear shallow disc cupping.

Safety of Fixed-Combination Bimatoprost 0.03%/Timolol 0.5% Ophthalmic Solution at 6 Months in Chinese Patients with Open-Angle Glaucoma or Ocular Hypertension.

INTRODUCTION: Fixed-combination bimatoprost 0.03%/timolol 0.5% ophthalmic solution (FCBT; Ganfort®, Allergan, an AbbVie company) effectively reduces intraocular pressure (IOP) via complementary mechanisms of action of the agents, but long-term (> 12 weeks) safety evaluations of FCBT remain limited. FCBT safety is evaluated herein, with particular focus on hyperemia and eyelash growth, at 24 weeks in Chinese patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). METHODS: In this multicenter, open-label, noncomparative, phase 4 study conducted in China, patients diagnosed with OAG or OHT having insufficient response to ß-blocker- or prostaglandin analogue/prostamide (PGA)-based IOP-lowering monotherapy in one or both eyes were switched from their current IOP-lowering treatment to FCBT (one drop per eye every evening) without prior washout. Assessment visits were scheduled at baseline and weeks 4, 12, and 24 (or study exit). The primary outcome measure was adverse event (AE) incidence through 24 weeks. RESULTS: Of 725 patients enrolled, 632 (87.2%) completed the study; 93 (12.8%) patients discontinued, including 29 (4.0%) due to AEs. Of 1326 FCBT-treated eyes (total), 594 (44.8%) experienced ≥ 1 ocular treatment-related AE during the study. Conjunctival hyperemia (the most common AE overall) and eyelash growth were reported in 269 (20.3%) and 54 (4.1%) FCBT-treated eyes, respectively. The incidence of other known PGA-related AEs (including blepharal pigmentation and erythema of eyelid) was < 10% each. Most conjunctival hyperemia reports were mild in severity (214/259; 82.6%) and only 1/259 (0.4%) was severe. Similarly, most cases of eyelash growth were mild (46/52; 88.5%); none were severe. One (< 0.1%) FCBT-treated eye had a serious ocular AE (OAG) considered FCBT-related. CONCLUSIONS: The frequency and severity of FCBT-related AEs, including conjunctival hyperemia and eyelash growth, are consistent with previously published findings. No new safety concerns were raised. This prospective study reaffirms that once-daily FCBT is a safe and well-tolerated therapy for OAG and OHT. GOV IDENTIFIER: NCT02571712.

Effect of Cluster Nursing on Recovery Effect and Hospitalization Time of Patients with Acute Cerebral Infarction After Thrombectomy.

Objective: To explore the effects of cluster nursing on self-care ability, length of hospital stay, complications and neurological function of patients with mechanical thrombectomy of large vessel occlusion in acute cerebral infarction. Methods: A total of 83 patients with acute cerebral infarction who underwent thrombolectomy in a tertiary hospital in Anhui Province from June 2019 to March 2021 were randomly divided into observation group and control group. The observation group was treated with cluster nursing intervention mode, and the control group was treated with routine nursing mode. Barthel index scores and National Institute of Health Stroke Scale (NIHSS) scores were compared between the two groups at admission and at 1 week, 1 month and 3 months of nursing intervention. The length of stay and incidence of complications were compared between the two groups. Results: There was no significant difference in baseline data, Barthel index and NIHSS score between the two groups at admission (P>0.05). The Barthel index at 1 week, 1 month and 3 months after operation in the observation group was significantly higher than that in the control group (P<0.05), while the NIHSS score, incidence of complications and length of hospital stay were significantly lower than those of the control group (P<0.05). Conclusion: Cluster nursing can improve the neurological function, improve the self-care ability, reduce the incidence of complications, shorten the hospitalization period, improve the prognosis and promote the recovery of patients with acute cerebral infarction thrombolysis.

Suprachoroidal injection of polyzwitterion hydrogel for treating glaucoma.

Glaucoma is the primary cause of irreversible blindness worldwide. The current treatments are primarily based on drug usage or surgical operation to reduce intraocular pressure (IOP). However, it is expensive and requires patients to insist on taking the medicine for a long time. The suprachoroidal space (SCS) is the space between the choroid and the sclera, which forms part of the uveovortex pathway in the circulation of aqueous humor. So far, it is still challenging to realize the injection of hydrogels into the SCS with long-term duration. In this work, an in situ-forming polyzwitterionic polycarboxybetaine hydrogel is designed and injected to expand SCS to increase the drainage of aqueous humor from the eye via the uveovortex pathway, thus reducing IOP for at least 6 weeks, while commercial hyaluronic acid hydrogel can only last for about 4 weeks. The clinical ophthalmological safety assessment examination shows that the treatment of polyzwitterion hydrogel is well-tolerated that leads to minimal inflammatory reaction, and histopathology assessment demonstrates that the SCS is expanded after injection of the hydrogel. Further analysis of ultrasound biomicroscopy reveals that there is a strong correlation between IOP reduction and SCS expansion. In short, the polyzwitterion hydrogel developed in this work can prolong the period of IOP reduction by expanding SCS, thus treating ocular hypertension and glaucoma without resorting to drugs or regular surgery.

Biometric indicators of anterior segment parameters before and after laser peripheral iridotomy by swept-source optical coherent tomography.

BACKGROUND: Primary angle closure glaucoma (PACG) is the most common type of glaucoma in China. Laser peripheral iridotomy (LPI) is the primary choice to treat PAC: We aim to evaluate the changes of biometric parameters of anterior segment and to find possible biometric predictors of the effect of laser peripheral iridotomy (LPI) in primary angle closure (PAC) eyes using swept-source optical coherent tomography (OCT). METHODS: LPI was performed in 52 PAC eyes of 28 participants. The change of intraocular pressure and anterior segment parameters, including angle opening distance (AOD500), AOD500 area, trabecular iris space area (TISA500), TISA500 volume, trabecular iris angle (TIA500), iridotrabecular contact (ITC) index, ITC area, anterior chamber volume (ACV), anterior chamber depth (ACD), lens vault (LV) and lens thickness (LT) before and 1 week after LPI were measured by Tomey CASIA2 anterior segment OCT. We also estimate and analyze potential associated factors possibly affecting the change of anterior chamber parameters. RESULTS: No post-laser complications were found. The ACD, LV and LT did not change significantly 1 week after LPI. AOD500, AOD500 area, TISA500, TISA500 volume, TIA500, ACV increased significantly after LPI. There was significant decrease in ITC index and ITC area. LT was positively correlated to the change of ITC index (ß = 0.239, *p = 0.045). CONCLUSIONS: The anterior segment architecture significantly changed after LPI in PAC spectrum eyes. Crystalline lens measurements remained unchanged before and after LPI. AS-OCT can be used to follow anterior chamber parameter changes in PAC spectrum eyes. LT may play a role in the therapeutic effect of LPI.

3D printed biomimetic epithelium/stroma bilayer hydrogel implant for corneal regeneration.

Corneal regeneration has always been a challenge due to its sophisticated structure and undesirable keratocyte-fibroblast transformation. Herein, we propose 3D printing of a biomimetic epithelium/stroma bilayer implant for corneal regeneration. Gelatin methacrylate (GelMA) and long-chain poly(ethylene glycol) diacrylate (PEGDA) are blended to form a two-component ink, which can be printed to different mechanically robust programmed PEGDA-GelMA objects by Digital Light Processing (DLP) printing technology, due to the toughening effect of crystalline crosslinks from long-chain PEGDA on GelMA hydrogel after photo-initiated copolymerization. The printed PEGDA-GelMA hydrogels support cell adhesion, proliferation, migration, meanwhile demonstrating a high light transmittance, and an appropriate swelling degree, nutrient permeation and degradation rate. A bi-layer dome-shaped corneal scaffold consisting of rabbit corneal epithelial cells (rCECs)-laden epithelia layer and rabbit adipose-derived mesenchymal stem cells (rASCs)-laden orthogonally aligned fibrous stroma layer can be printed out with a high fidelity and robustly surgical handling ability. This bi-layer cells-laden corneal scaffold is applied in a rabbit keratoplasty model. The post-operative outcome reveals efficient sealing of corneal defects, re-epithelialization and stromal regeneration. The concerted effects of microstructure of 3D printed corneal scaffold and precisely located cells in epithelia and stroma layer provide an optimal topographical and biological microenvironment for corneal regeneration.

A Comparison of Face-Down Positioning and Adjustable Positioning After Pars Plana Vitrectomy for Macular Hole Retinal Detachment in High Myopia.

PURPOSE: To compare the anatomical and functional outcomes of macular hole retinal detachment (MHRD) in high myopia after pars plana vitrectomy (PPV) with face-down positioning and adjustable positioning. METHODS: Fifty-three eyes from 53 patients with MHRD were analyzed in this study. All patients received PPV with silicon oil for tamponade and then subdivided into 2 groups: 28 were included in a face-down positioning group and 25 were included in the adjustable positioning group. Patients were followed up for at least 6 months. The main outcome was the rate of anatomical macular hole (MH) closure and retinal reattachment. Secondary outcome measures were the best-corrected visual acuity and postoperative complications. RESULTS: There was no significant difference in the rate of MH closure (53.6 vs. 72.0%, p = 0.167) and retinal reattachment (100 vs. 96%, p = 0.472) between the face-down group and adjustable group. Compared with the mean preoperative best-corrected visual acuity (BCVA), the mean postoperative BCVA at the 6-month follow-up improved significantly in both groups (p = 0, both). But there was no significant difference in the mean postoperative BCVA (p = 0.102) and mean BCVA improvement (p = 0.554) at 6 months after surgery between the two groups. There was no significant difference in the high intraocular pressure (IOP) after surgery between the two groups (53.6 vs. 44%, p = 0.487). There were no other complications that occurred during the follow-up. CONCLUSION: Adjustable positioning after PPV with silicon oil tamponade for MHRD repair is effective and safe. Face-down positioning does not seem to be necessary for all patients with MHRD.

Long-Term Effects of a Photodisruptive Laser-Induced Traumatic Neuropathy Model.

Purpose: To create a mouse traumatic optic neuropathy (TON) model that is reproducible, reliable, and easy to manipulate with high specificity to retinal ganglion cell (RGC) layer and no mortality. The model will be useful for understanding the pathophysiology of retinal ganglion cell death and for testing neuroprotective therapeutics. Methods: An Nd:YAG laser was used to generate focal photodisruptive retinal damage. Noninvasive in vivo ophthalmologic imaging technologies such as optical coherence tomography (OCT) and confocal laser scanning ophthalmoscopy (CSLO) were used to longitudinally track the retinal nerve fiber layer (RNFL) thickness and RGC number change, respectively. Immunostaining and pattern electroretinography (PERG) were also used to evaluate structure and functional change after laser injury. Results: Our ND:YAG laser generates a concussive photodisruptive laser shockwave force which induces focal RGC death in the targeted area. We observed a correlative decrease in RGCs number, RNFL, and PERG function of RGC in the laser zone. The pattern of RNFL thinning and RGC soma loss correlates with the pattern and amount of fluorescence loss on OCT and CSLO images, respectively. The ND:YAG laser does not cause any damage to other layers in the retina nor any side effects including changes in intraocular pressure, corneal edema, and calcification or mortality (which has been observed in other TON models). Conclusions: We have created a new and novel RGC TON death model that confers no mortality and produces a quantifiable decrease in RGC number and function. The laser targeted regions of the retina correlate with both in vivo imaging by OCT and CSLO and histologically with regions of RGC loss without ophthalmic side effects. Translational Relevance: This laser-based TON injury model is simple to implement, is reproducible, and is useful for determining the molecular and cellular pathophysiology of TON and RGC death and for testing neuroprotective therapeutics.

An in situ-forming polyzwitterion hydrogel: Towards vitreous substitute application.

Development of a biostable and biosafe vitreous substitute is highly desirable, but remains a grand challenge. Herein, we propose a novel strategy for constructing a readily administered vitreous substitute based on a thiol-acrylate clickable polyzwitterion macromonomer. A biocompatible multivinyl polycarboxybetaine (PCB-OAA) macromonomer is designed and synthesized, and mixed with dithiothreitol (DTT) via a Michael addition reaction to form a hydrogel in vitreous cavity. This resultant PCB-OAA hydrogel exhibits controllable gelation time, super anti-fouling ability against proteins and cells, excellent biocompatibility, and approximate key parameters to human vitreous body including equilibrium water content, density, optical properties, modulus. Remarkably, outperforming clinically used silicone oil in biocompatibility, this rapidly formed hydrogel in the vitreous cavity of rabbit eyes remains stable in vitreous cavity, showing an appealing ability to prevent significantly inflammatory response, fibrosis and complications such as raised intraocular pressure (IOP), and cataract formation. This zwitterionic polymer hydrogel holds great potential as a vitreous substitute.

Contributions of prelimbic cortex, dorsal and ventral hippocampus, and basolateral amygdala to fear return induced by elevated platform stress in rats.

Fear relapse is a major challenge in the treatment of stress-related mental disorders. Most investigations have focused on fear return induced by stimuli associated with the initial fear learning, while little attention has been paid to fear return evoked after exposure to an unconditioned stressor. This study explored the neural mechanisms of fear return induced by elevated platform (EP) stressor in Sprague-Dawley rats initially subjected to auditory fear conditioning. The contributions of the prelimbic cortex (PL), dorsal hippocampus (DH), ventral hippocampus (VH), and basolateral amygdala (BLA) were examined by targeted bilateral intracerebral injection of the GABAA agonist muscimol after elevated platform (EP) stressor. Muscimol-induced inactivation of PL or BLA significantly impaired the return of conditioning fear, while inactivation of the DH or VH had no effect. These results suggest that fear return induced by non-associative stressor may depend on the PL and BLA but not on the hippocampus.

lncRNA TGFß2-AS1 promotes ECM production via TGF-ß2 in human trabecular meshwork cells.

Evidence indicates that long noncoding RNAs (lncRNAs) participate in the regulation of various physiological and pathological processes including organ fibrosis and eye-related diseases. The important pathological manifestations of open-angle glaucoma (OAG) are human trabecular meshwork cells (HTMCs) apoptosis and excessive deposition of extracellular matrix (ECM) components in TM, which can cause pathological changes in the outflow pathway. To investigate the role and regulation mechanism of lncRNA in HTMCs under oxidative stress, we established an oxidative stress model in HTMCs using hydrogen peroxide (H2O2) followed by RNA sequencing and found that subsets of lncRNAs and mRNAs that closely associate with TGF-ß signaling are differentially regulated in these cells. We then constructed a network with the TGF-ß2 -colocalized and -coexpressed lncRNAs, to investigate the effects and regulatory mechanisms of the potential lncRNAs on ECM deposition in HTMCs. The gain-of-function and loss-of-function experiments demonstrated that lnc-TGFß2-AS1 promotes ECM production via TGF-ß2 in HTMC, suggesting that lnc-TGFß2-AS1 may be a potential glaucoma treatment target.

Biometric indicators of eyes with occult lens subluxation inducing secondary acute angle closure.

BACKGROUND: To compare the anterior biometrics in eyes with secondary acute angle closure induced by occult lens subluxation (ASAC-LS), misdiagnosed as acute primary angle closure (APAC) at the first visit with APAC, chronic primary angle closure glaucoma (CPACG), and cataract. METHODS: This retrospective case study included 17 eyes with angel closure due to occult LS, who were misdiagnosed as APAC on their first visit, 56 APAC eyes, 54 CPACG eyes, and 56 cataract eyes. Axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), aqueous depth (AD) and lens thickness (LT) were recorded. Lens position (LP), relative lens position (RLP), corrected lens position (CLP) were calculated. Quantitative data were subject to one-way analysis of variance and correlation analysis. Categorical data were analyzed using the chi-squared test. Receiver operating characteristic (ROC) curves were plotted to obtain a suitable cutoff value of ocular biometrics. RESULTS: The ASAC-LS patients had a longer ocular axial length than APAC and CPACG patients. Central corneal thickness of the ASAC-LS patients was not significantly different from APAC patients, but was significantly different from CPACG and cataract patients. The APAC patients had the smallest ACD, while the ASAC-LS patients had the smallest AD. The ASAC-LS patients had the largest lens thickness. According to ROC curve analysis, RLP, ACD, AD, CLP, LP had high power of discrimination. CONCLUSIONS: This study revealed that LS secondary PAC patients had a shallower AD, thicker CCT comparing to those of APAC, CPACG and cataract patients. For patients with acute angle-closure glaucoma, it is necessary to exclude lens zonula relaxation. TRIAL REGISTRATION: NCT03752710, retrospectively registered.

1α,25-dihydroxyvitamin D3 attenuates oxidative stress-induced damage in human trabecular meshwork cells by inhibiting TGFß-SMAD3-VDR pathway.

Evidence indicates that 1α, 25-dihydroxy vitamin D3 (1, 25-(OH)2D3) markedly reduces intraocular pressure (IOP) in nonhuman primates, while the biochemical mechanisms are unclear. To investigate the influence of oxidative stress on human trabecular meshwork cells (HTMCs) and the effect and regulatory mechanism of 1, 25-(OH)2D3 in HTMCs under oxidative stress, we established an oxidative stress model in HTMCs using hydrogen peroxide (H2O2) and showed that 1, 25-(OH)2D3 could inhibit oxidative stress-induced apoptosis and reduce extracellular matrix (ECM) composition of HTMCs. Moreover, 1, 25-(OH)2D3 could attenuate H2O2-induced inflammation in HTMCs. Mechanistically, our findings revealed that H2O2-induced damage was mediated by the transforming growth factor-ß (TGF-ß)-SMAD3 pathway in HTMCs, and 1, 25-(OH)2D3 could protect HTMCs against oxidative stress through vitamin D receptor (VDR), which antagonises the effects of SMAD3. Overall, these findings define a mechanism by which 1, 25-(OH)2D3 reduces ECM accumulation and suppresses the TGF-ß-SMAD3-VDR pathway in HTMCs, thus protecting the cells from oxidative stress, suggesting 1, 25-(OH)2D3 might be a potential therapeutic for glaucoma.