A glaucoma micro-stent with diverging channel and stepped shaft structure based on microfluidic template processing technology.

BACKGROUND: Minimally invasive glaucoma surgery (MIGS) has experienced a surge in popularity in recent years. Glaucoma micro-stents serve as the foundation for these minimally invasive procedures. Nevertheless, the utilization of these stents still presents certain short-term and long-term complications. This study aims to elucidate the creation of a novel drainage stent implant featuring a diverging channel, produced through microfluidic template processing technology. Additionally, an analysis of the mechanical properties, biocompatibility, and feasibility of implantation is conducted. RESULTS: The stress concentration value of the proposed stent is significantly lower, approximately two to three times smaller, compared to the currently available commercial XEN gel stent. This indicates a stronger resistance to bending in theory. Theoretical calculations further reveal that the initial drainage efficiency of the gradient diverging drainage stent is approximately 5.76 times higher than that of XEN stents. Notably, in vivo experiments conducted at the third month demonstrate a favorable biocompatibility profile without any observed cytotoxicity. Additionally, the drainage stent exhibits excellent material stability in an in vitro simulation environment. CONCLUSIONS: In summary, the diverging drainage stent presents a novel approach to the cost-effective and efficient preparation process of minimally invasive glaucoma surgery (MIGS) devices, offering additional filtering treatment options for glaucoma.

Investigating the uncertain causal link between gut microbiota and glaucoma: A genetic correlation and Mendelian randomisation study.

BACKGROUND: Glaucoma is the most common cause of irreversible blindness, and gut microbiota (GM) is associated with glaucoma. Whether this association represents a causal role remains unknown. This study aims to assess the potential association and causal link between GM and various forms of glaucoma, emphasising the need for cautious interpretation of the strength of these associations. METHODS: Employing a two-sample bidirectional Mendelian randomisation (MR) framework with false discovery rate correction and various sensitivity analyses, supplemented by genetic correlation analysis via linkage disequilibrium score regression (LDSC) and colocalisation for European summary-level data between MiBioGen consortium and FinnGen Study, we sought to explore the relationship between GM and glaucoma. RESULTS: While certain microbial taxa showed potential associations with glaucoma subtypes (e.g., Erysipelotrichaceae with primary angle closure glaucoma, Senegalimassilia with exfoliation glaucoma), the overall findings suggest a complex and not definitively causal relationship between GM and glaucoma. Notably, reverse MR analysis did not establish a significant causal effect of glaucoma on GM composition, and no consistent genetic correlations were observed between GM and glaucoma. CONCLUSIONS: While our study provides some evidence of associations between specific GM taxa and glaucoma, the results underscore the complexity of these relationships and the need for further research to clarify the potential causal links. The findings highlight the importance of interpreting the gut-eye axis with caution and suggest that while GM may play a role in glaucoma, it is unlikely to be a predominant causal factor.

The Agreement of the Nomogram Tool and Ultrasound Biomicroscopy Images in Calculating Ultrasound Cycloplasty Probe Model in Chinese Patients.

PURPOSE: The aim of the study was to compare and explore the agreement between the nomogram tool and ultrasound biomicroscopy (UBM) images method to calculate the ultrasound cycloplasty (UCP) probe model in Chinese glaucoma patients. METHODS: Retrospective analysis of Chinese glaucoma patients who visited Zhongshan Ophthalmic Center in Guangzhou from January to December 2019 and were eligible for UCP surgery. Visual acuity, intraocular pressure (IOP), ocular axial length (AL), and horizontal corneal diameter (white to white [WTW]) were measured. UBM images with clear ciliary body imaging and AL and WTW data were sent to trained personnel for probe model measurements. The data calculated by both methods were analyzed using unweighted and weighted κ statistics. The level of agreement refers to Landis and Koch's guideline for the strength of agreement indicated with weighted κ values. RESULTS: 1,061 eyes of 642 patients were involved, with a mean age of 61.66 ± 11.66 years. Their best-corrected visual acuity converted to logarithm of minimal-angle-of-resolution (logMAR) scores of -0.18-3.00 with a mean value of 0.69 ± 0.77. IOP was 22.0-60.0 mm Hg with a mean of 27.97 ± 5.66 mm Hg. The mean AL and WTW were 22.88 ± 1.33 (19.15-32.14) mm and 11.52 ± 0.49 (10.00-12.90) mm, respectively. The agreement between the two methods was fair (weighted κ = 0.299), matching in 62.86% of eyes (weighted κ = 0.299, κ = 0.264). The agreement in primary open angle glaucoma, acute primary angle-closure glaucoma, chronic primary angle-closure glaucoma, and secondary glaucoma patients was 60.85% (weighted κ = 0.336, κ = 0.301), 65.06% (weighted κ = 0.146, κ = 0.127), 62.26% (weighted κ = 0.204, κ = 0.184), and 57.97% (weighted κ = 0.332, κ = 0.280) of eyes, respectively. CONCLUSION: The agreement between UBM images and the nomogram tool to calculate the UCP probe model of Chinese patients is at a fair level. The nomogram tool prefers to use larger probes. Improvements to the nomogram tool, such as including data from more ethnic groups and being able to calculate separately for different types of glaucoma, are needed to improve accuracy. The inclusion of parameters or images from more directions of the eye may help measure probe models more accurately for both the nomogram tool and the UBM image measurement.

Distribution of ultrasound cyclo plasty probe models in Chinese patients with glaucoma.

PURPOSE: To investigate the distribution of ultrasound cyclo plasty (UCP) probe models in Chinese patients with glaucoma. METHODS: Patients needing glaucoma surgery were recruited at Zhongshan Ophthalmic Center from January 2019 to December 2019. Patient demographics were recorded and analyzed. Visual acuity, intraocular pressure (IOP), retinal nerve fiber layer (RNFL), mean defect of visual field (MD), ocular axial length (AL) and horizontal corneal diameter (white to white, WTW) of eyes with glaucoma were measured. In addition, the UCP probe models were calculated using a nomogram tool and two ocular anatomical parameters: WTW and AL. RESULTS: A total of 1281 patients (2000 eyes) were included in the study, including 559 males (43.64%) and 722 females (56.36%). The age of the patients ranged from 18 to 91 years, with a mean age of 61.43 ± 12.21 years. IOP ranged from 22.0 to 60.0 mmHg, with a mean of 26.17 ± 3.52 mmHg. The mean AL and WTW were 22.96 ± 1.43 (ranging from 19.07 to 35.00) and 11.55 ± 0.50 (ranging from 9.6 to 13.7), respectively. According to the results calculated by the nomogram tool, Chinese patients' eyes mainly adapted to Model 12, with a percentage of 69.05%. Model 13 and Model 11 were suitable for 26.65% and 3.35% of the patients, respectively. A total of 0.95% of Chinese patients did not have a suitable probe model. CONCLUSION: For Chinese patients who needed glaucoma surgery, UCP probe models were mainly attributed to Model 12, followed by Model 13, and Model 11 was the least used.

TCF7L2 promotes ER stress signaling in diabetic retinopathy.

Diabetic retinopathy (DR) is one of the most common blindness in working-age adults. Transcription factor 7 like 2 (TCF7L2) is a susceptibility gene of DR, however, its roles in the pathogenesis of DR are still largely unknown. In this study, we found that TCF7L2 was mainly located in the cell nucleus of retinal ganglion cell layer (GCL) and inner nuclear layer (INL), while it was not expressed in the cell nucleus of retinal outer nuclear layer (ONL). Expression of TCF7L2 was significantly elevated in the retinas of db/db diabetic mice and oxygen-induced retinopathy (OIR) mice. Also, in Ad-hTCF7L2 treated hiPSCs-derived retinal progenitor cells (RPCs), activating transcription factor 6 (ATF6)-related endoplasmic reticulum (ER) stress signaling was remarkably activated. Moreover, knockdown of TCF7L2 significantly inhibited ATF6-related ER stress signaling. Furthermore, the data of endothelial permeability assay showed that RPCs pretreated with Ad-hTCF7L2 lead to enhanced monolayer permeability of human umbilical vein endothelial cells (HUVECs), and knockdown of TCF7L2 or ATF6 in RPCs could alleviate the monolayer permeability of HUVECs. Thus, our results showed that TCF7L2 could trigger ATF6-related ER stress signaling and promote vein endothelial cell permeability, which will provide important insight into the role of TCF7L2 in the pathogenesis of DR and contribute to designing potential therapies.

The profile of gut microbiota and central carbon-related metabolites in primary angle-closure glaucoma patients.

PURPOSE: To explore the profile of gut microbiota and central carbon-related metabolites in patients with primary angle-closure glaucoma (PACG). METHODS: The fecal microbiotas of 30 PACG patients and 30 healthy participants were detected via 16S rRNA sequencing. Targeted liquid chromatography-mass spectrometry was used to examine serum central carbon-related metabolites. The correlations among metabolites, microbiotas and clinical presentations were also explored. RESULTS: Although the α and ß diversity between the PACG and control groups did not show a significant difference, the distribution of Blautia and Fusicatenibacter decreased significantly in the PACG group. Functional annotations of microbiota enrichment showed that the most dominant pathway was related to host metabolism. In the PACG patients, seven central carbon metabolites, namely adenosine 5'-diphosphate, dGDP, phosphoenolpyruvic acid, d-ribulose 5-phosphate, d-xylulose 5-phosphate, glucuronic acid, and malonic acid, decreased significantly, whereas two metabolites, citric acid and isocitrate, increased obviously. The mean RNFL thickness was positively correlated with phosphoenolpyruvic acid, the VF-MD was positively correlated with glucuronic acid, and the abundance of Blautia was negatively associated with citric acid. CONCLUSION: Few species of gut microbiota were altered in the PACG patients compared to the healthy subjects. A distinct difference in the phenotype of the central carbon-related metabolites of PACG and their correlation with clinical presentations and microbiota suggests potential mechanisms of RGC impairment and novel intervention targets.

A Comparison of Subconjunctival Wound Healing between Different Methods of Dissecting Subconjunctival Tissues.

OBJECTIVE: To compare different methods for dissecting subconjunctival tissues by developing subconjunctival wound healing models. METHODS: New Zealand white rabbits were separated into 3 groups based on the method by which the rabbit subconjunctival wound healing model was generated: subconjunctival tissues were dissected episclerally (EPI) or subepithelially (SUB), with a corresponding blank control (CON). All the cases in the experimental groups were surgically prepared with conjunctival flaps, and they were sacrificed on the third postoperative day. At the surgical sites, the protein levels of hypoxia-inducible factor-1 (HIF-1)-α, vascular endothelial growth factor (VEGF)-A, and matrix metalloproteinase (MMP)-2 were detected by Western blot, morphological vascularity was measured by Adobe Photoshop, and subconjunctival fibrosis was assessed by histology. RESULTS: Compared with the CON group, both the EPI and SUB groups showed significantly upregulated protein levels of HIF-1α, VEGF-A, and MMP-2. In addition, the protein levels of HIF-1α, VEGF-A, and MMP-2 were higher in the EPI group than in the SUB group. Morphological vascularity was significantly elevated in the EPI group compared with the SUB and CON groups. Collagen content was markedly increased in the EPI group compared with the SUB and CON groups. CONCLUSIONS: Dissecting subconjunctival tissues subepithelially inhibits subconjunctival fibrosis, which may be instructive in tenonectomy in filtration surgery.

Gut microbiota compositional profile and serum metabolic phenotype in patients with primary open-angle glaucoma.

The gut microbiota (GM) and its influence on host metabolism are considered to be an environmental factor that contributes to the progression of many immune and neurodegenerative diseases. However, the features of the GM and serum metabolites in Primary open-angle glaucoma (POAG) patients have not been clearly elucidated. The purpose of this research is to explore the gut microbial composition and serum metabolic phenotype in POAG patients. 16S rRNA V4 genes of bacteria from the fecal samples of 30 POAG patients and 30 healthy subjects were sequenced by the Illumina MiSeq platform and then analyzed by QIIME. Their serum samples were analyzed by gas chromatography/mass spectrometry (GC-MS)-based metabolomics. The association between gut microbial species and host circulating metabolites and clinical phenotypes was also analyzed. Compared with controls, f Prevotellaceae, g unidentified Enterobacteriaceae, and s Escherichia coli increased the most in POAG patients, whereas g Megamonas and s Bacteroides plebeius significantly decreased in POAG patients. The alteration of the endogenous metabolomic profile in POAG patients included five amino acids or dipeptides, two hormone derivates, one purine derivative, one bile acid derivative and one organic acid. It also showed that citric acid was positively correlated with Megamonas, whereas L-γ-Glutamyl-L-alanine, MHPG, cholic acid glucuronide and hypoxanthine were negatively correlated with Megamonas. Mean visual acuity was negatively correlated with Blautia, mean VF-MD was negatively correlated with Faecalibacterium, and average RNFL thickness was positively correlated with Streptococcus. Our results revealed that there was a distinct difference in GM composition and serum metabolic phenotype between POAG patients and healthy individuals. This finding suggests the potential correlations between the GM and serum metabolites in the pathogenesis of glaucoma and thus provides new insight into the GM-targeted interventions of this disease.

One-month IOP in mitomycin C-augmented trabeculectomy can predict long-term IOP control in chronic primary angle-closure glaucoma.

PURPOSE: To investigate the predictors of long-term intraocular pressure (IOP) in chronic primary angle-closure glaucoma (CPACG) treated with primary trabeculectomy. METHODS: This study systematically reviewed cases of CPACG treated with primary trabeculectomy. The scleral flaps in all cases were sutured with two stitches in situ and two releasable sutures to ensure watertight under normal IOP conditions during surgery. Mitomycin C was used in all eyes. All patients were followed for 2 years. Digital massage of the bulbus and removal of the releasable suture were performed according to the IOP and shape of the filtering bleb. Demographic data and clinical outcomes were recorded. Factors predicting long-term IOP were identified. RESULTS: A total of 72 patients (88 eyes) with a mean age of 58.51 ± 10.60 years were included in this study. The complete success rate was 89.77% after 2 years. The IOP began to stabilize after 7 days and reached its lowest point at the 1-month follow-up. The preoperative and early postoperative high or low IOP does not affect long-term effects (P > 0.05). There was a positive correlation between postoperative IOP at the 1-month and 2-year follow-ups (r = 0.64, P < 0.001). CONCLUSION: In CPACG patients undergoing primary trabeculectomy, scleral flaps sutured watertightly with two stitches in situ and two releasable sutures under normal IOP conditions can ensure controllable, effective and safe treatment of CPACG. The preoperative and early postoperative high or low IOP does not affect long-term effects. One-month postoperative IOP can be used as a predictor of long-term IOP control.

Posttraumatic glaucoma in southern China: A ten-year retrospective study.

PURPOSE: To analyze posttraumatic glaucoma regarding its demographics, presentations, different causes, surgical modalities, and hospitalization burden among patients in southern China. METHODS: This retrospective study investigated all individuals with posttraumatic glaucoma admitted to the Zhongshan Ophthalmic Center of Sun Yat-Sen University from January 2012 through December 2021. RESULTS: Out of 2211 cases, 64.82% had closed globe injury (CGI), 28.22% had open globe injury (OGI), and 6.96% had chemical injury (CI). The mean age of all patients was 44.45 ± 19.45 years old. Males (83.36%), rural patients (56.17%), and farmers (27.14%) predominantly had posttraumatic glaucoma. The most common external injury mechanism was blunt objects (37.82%). Compared with the other two groups, the majority of surgical modalities were cataract extraction (27.12%) in the CGI group, combined anterior-posterior surgery (34.79%) in the OGI group, and cyclocryotherapy/cyclophotoagulation (49.1%) in the CI group. The CI group had higher times of hospitalization (3.542 ± 0.242) and hospitalization duration (8.373 ± 0.743 days), whereas the OGI group had more operation expense ($ 1476.729 ± 11.047) and medical consumables expense per head ($ 962.578 ± 25.801). CONCLUSION: Blunt injury, males, adults, farmers, and rural patients were high-risk factors for posttraumatic glaucoma. Chemical-induced glaucoma management requires a longer hospitalization period, while OGI requires more medical expenditure. This knowledge provides a new reference for clinicians to accurately diagnose and intervene in posttraumatic glaucoma. It also suggests that more education and long-term surveillance are needed regarding the presence of glaucoma after ocular trauma.

The Mechanisms and Application Value of Postbiotics in Caries Prevention and Management.

Dental caries, one of the most prevalent diseases globally, affects individuals throughout their lifetimes. Recently, researchers have increasingly focused on postbiotics for caries prevention. Postbiotics, comprising inanimate microorganisms and/or their components, confer health benefits to the host. Growing evidence suggests postbiotics' potential anticaries effects. Specifically, numerous postbiotics have demonstrated the ability to inhibit dental caries onset and progression by modulating oral flora microecology and reducing human caries susceptibility. This review elaborates on the current research regarding postbiotics' anticaries effects, highlights some studies' shortcomings, and innovatively proposes that postbiotics could potentially influence tooth development and salivary characteristics through epigenetic modifications. Furthermore, it anticipates postbiotics' future application in personalised caries treatment, given their multifaceted anticaries potential.

The Burden and Clinical Features of Neovascular Glaucoma in A Major Tertiary Care Center in China.

PRCIS: This research presents the burden and clinical characteristics of NVG in Zhongshan Ophthalmic Center, employing the most extensive sample size and the longest uninterrupted temporal duration so far, which may provide a theoretical reference for the effective prevention and diagnosis of NVG. PURPOSE: To summarize the burden and clinical characteristics of neovascular glaucoma (NVG) in a major tertiary care center in China. METHODS: The clinical data of NVG patients in Zhongshan Ophthalmic Center (ZOC) between 2012 and 2021 were collected retrospectively, including their age, sex, affected eye, best-corrected visual acuity (BCVA), intraocular pressure (IOP), clinical stage and aetiology. RESULTS: In this study, we included 1877 eyes of 1749 patients who developed NVG, with 2.01:1 ratio of male to female. Their mean age was 53.14±16.69 years and those aged 41-70 years (65.2%) were most affected. Monocular patients were more predominant in most of them (92.7%), while 7.3% were binocular and 1667 eyes (88.8%) were at the angle­closure stage. The BCVA and IOP were 2.42±0.70 logMAR and 38.6±12.2 mmHg, respectively. Over the decade, the number of NVG patients and the proportion of NVG patients among glaucoma patients showed an increasing trend, with annual percentage changes (APCs) of 9.1% (95% CI: 5.0-13.3%, P=0.001) and 4.8% (95% CI: 2.2-7.4%, P=0.003), respectively. The top three primary conditions were diabetic retinopathy (DR), retinal vein occlusion (RVO), and retinal detachment (RD). Moreover, the APCs for the constituent ratio of DR and RVO were 4.4% (95% CI: 0.5-8.4%, P=0.031) and ï¹£4.6% (95% CI: ï¹£8.4% to ï¹£0.7%, P=0.028), respectively. However, the first and second causes of NVG in minors (<18 years old) were Coat's disease and ocular tumours, followed by RD and RVO in third place. The top cause of NVG in patients aged 65 years and older was RVO. CONCLUSIONS: The burden of NVG is increasing, emphasizing the need to improve preventive strategies focusing on primary diseases such as DR, RVO, and RD, particularly the increasing proportion of DR cases and the previously underemphasized RD patients, while also highlighting the differences in primary diseases across different age groups.

The Macular Pigment Optical Density (MPOD) Decrease in Chinese Primary Angle Closure Glaucoma Using the One-Wavelength Reflectometry Method.

PURPOSE: The objective of this study was to observe the macular pigment optical density (MPOD) and the relationship between MPOD and retinal thickness in Chinese primary angle-closure glaucoma (PACG) patients by the one-wavelength reflectometry method. METHODS: This study was a prospective comparative observational study, including 39 eyes from 39 PACG patients (15 men and 24 women, mean age 61.89 ± 12.30) and 41 eyes from 41 controls (20 men and 21 women, mean age 63.24 ± 14.02). We measured the MPOD 7-degree area by the one-wavelength reflectometry method and analyzed both the max and mean optical density (OD). The central retinal thickness (CRT) and the total thickness of the macular ganglion cell layer (GCL), and inner plexiform layer (IPL)were measured by spectral-domain-optical coherence tomography (SD-OCT). Statistical methods such as Shapiro-Wilk test, Fisher's exact test, chi-square test, two independent samples test and Spearman's correlation coefficient were used to observe the differences in the MPOD between normal subjects and PACG patients and the correlation between the MPOD and retinal thickness. RESULTS: The max optical density (Max OD) (PACG group: 0.302 ± 0.067d.u, control group: 0.372 ± 0.059d.u., p < .001) and mean optical density (Mean OD) (PACG group: 0.124 ± 0.035d.u., control group: 0.141 ± 0.028d.u., p < 0.05) were significantly reduced in PACG patients compared with control subjects. Significant decreases in GCL + IPL thickness (PACG group: 74.71 ± 39.56 µm, control group:113.61 ± 8.14 µm, p < 0.001) and CRT (PACG group: 254.49 ± 41.47 µm, control group:329.10 ± 18.57 µm, p < 0.001) were also observed in PACG eyes. There was no statistically significant correlation between the MPOD and GCL + IPL thickness (p = .639, p = .828). CONCLUSIONS: MPOD was significantly lower in Chinese PACG patients than in the control group, potentially due to thinning of the GCL + IPL thickness. This study provides insights for the pathophysiology, assessment of PACG and potential guidance for lifestyle modifications.

In this study, we measured the MPOD values of Chinese PACG patients for the first time using the one-wavelength reflectance method and clarified that the MPOD of PACG patients was significantly lower than that of the normal group. This study provides insights for the pathophysiology, assessment of PACG and potential guidance for lifestyle modifications.

Noncontact Conjunctiva: A Better Mitomycin C Application Site for Trabeculectomy.

INTRODUCTION: Bleb scarring is the most important complication of trabeculectomy. Changing the application position of mitomycin C (MMC) during trabeculectomy might affect the surgery outcome. Our aim is to compare the effectiveness and safety of intraocular pressure (IOP) lowering in two different application sites of mitomycin in trabeculectomy. METHODS: This retrospective trial compared the surgical outcomes of 177 eyes that underwent trabeculectomy with adjunctive mitomycin C. In 70 eyes, an MMC-soaked sponge was applied under the scleral flap without touching Tenon's capsule. In 107 eyes, an MMC-soaked sponge was applied under the scleral flap covered by Tenon's capsule. Outcome measures were the IOP, best-corrected visual acuity (BCVA), success rates, and incidence of complications. RESULTS: Within both groups, a highly significant IOP reduction was seen during follow-up. The effectiveness in reducing IOP and the change in best-corrected visual acuity (BCVA) were similar between the two groups. Thin-walled blebs and postoperative hypotony were seen more often when MMC-soaked sponges were applied under the scleral flap covered by Tenon's capsule (P = 0.008 and P = 0.012, respectively). There was no significant difference in BCVA or other complications in either group. CONCLUSION: Since the effectiveness of IOP reduction was similar between both groups and with a low incidence of thin-walled blebs and hypotony, the subscleral application without touching Tenon's capsule seems to be the safer application site of MMC during trabeculectomy.

Lipocalin 2 induces visual impairment by promoting ferroptosis in retinal ischemia-reperfusion injury.

Background: Retinal ischemia-reperfusion (RIR) is a common pathological condition that can lead to retinal ganglion cell (RGC) death and visual impairment. However, the pathogenesis of RGC loss and visual impairment caused by retinal ischemia remains unclear. Methods: A mouse model of elevated intraocular pressure (IOP)-induced RIR injury was used. Flash visual evoked potentials (FVEPs) and electroretinography (ERG) recordings were performed to assess visual function. The structural integrity of the retina and the number of RGC were assessed using hematoxylin and eosin (HE) staining and retinal flat mounts. Ferroptosis was evaluated by testing the levels of glutathione (GSH), malondialdehyde (MDA), glutathione peroxidase (GPX4), and ferritin light chains (FTL) in the retina of wild-type (WT) and lipocalin-2 transgenic (LCN2-TG) mice after RIR injury. Results: We found that LCN2 was mainly expressed in the RGC layer in the retina of wild-type mice and remarkably upregulated after RIR injury. Compared with wild-type mice, aggravated RGC death and visual impairment were exhibited in LCN2-TG mice with RIR injury. Moreover, LCN2 overexpression activated glial cells and upregulated proinflammatory factors. More importantly, we found that LCN2 strongly promoted ferroptosis signaling in RGC death and visual impairment. Liproxstatin-1, an inhibitor of ferroptosis, could significantly ameliorate RGC death and visual impairment. Furthermore, we found significantly alleviated RGC death and retinal damage in LCN2 heterozygous knockout mice. Conclusions: Our study provides important insights linking upregulated LCN2-mediated promotion of ferroptosis to RGC death and visual function impairment in the pathogenesis of ischemic retinopathy.

PLSCR1 promotes apoptosis and clearance of retinal ganglion cells in glaucoma pathogenesis.

Glaucoma is the leading cause of irreversible blindness worldwide. In the pathogenesis of glaucoma, activated microglia can lead to retinal ganglion cells (RGCs) apoptosis and death, however, the molecular mechanisms remain largely unknown. We demonstrate that phospholipid scramblase 1 (PLSCR1) is a key regulator promoting RGCs apoptosis and their clearance by microglia. As evidenced in retinal progenitor cells and RGCs of the acute ocular hypertension (AOH) mouse model, overexpressed PLSCR1 induced its translocation from the nucleus to the cytoplasm and cytomembrane, as well as elevated phosphatidylserine exposure and reactive oxygen species generation with subsequent RGCs apoptosis and death. These damages were effectively attenuated by PLSCR1 inhibition. In the AOH model, PLSCR1 led to an increase in M1 type microglia activation and retinal neuroinflammation. Upregulation of PLSCR1 resulted in strongly elevated phagocytosis of apoptotic RGCs by activated microglia. Taken together, our study provides important insights linking activated microglia to RGCs death in the glaucoma pathogenesis and other RGC-related neurodegenerative diseases.

Safety profile of 0.0015% tafluprost eye drops in China: a post-marketing observational study.

AIM: To investigate the treatment pattern and safety of tafluprost for glaucoma and ocular hypertension (OH) in clinical practice in China. METHODS: This post-marketing observational study included patients who received tafluprost to lower intraocular pressure (IOP) within 30d between September 2017 and March 2020 in 20 hospitals in China. Adverse drug reactions (ADRs) during tafluprost treatment and within 30d after the treatment were collected. RESULTS: A total of 2544 patients were included in this study, of them 58.5% (1488/2544) had primary open angle glaucoma (POAG), 21.9% (556/2544) had OH and 19.7% (500/2544) used tafluprost for other reasons. Of 359 ADRs occurred in 10.1% (258/2544) patients, and no serious adverse event occurred. The most common ADR was conjunctival hyperemia (128 ADRs in 124 patients, 4.9%). Totally 1670 participants (65.6%) combined tafluprost with carbonic anhydrase inhibitors (CAIs; 37.1%, 620/1670), sympathomimetics (33.5%, 559/1670), ß-blockers (33.2%, 555/1670), other prostaglandin analogs (PGAs; 15.6%, 260/1670) and other eye drops (15.1%, 253/1670). The highest incidence of conjunctival hyperemia was noted in patients who received tafluprost in combination with other PGAs (23 ADRs in 23 patients, 8.8%, 23/260) and the lowest was in combination with CAIs (16 ADRs in 16 patients, 2.6%, 16/620). Tafluprost was applied in primary angle-closure glaucoma (41.6%, 208/500), after glaucoma surgery (17.8%, 89/500) and after non-glaucoma surgery (15.8%, 79/500). CONCLUSION: Tafluprost is safe for POAG and OH, and tolerable when combined with other eye drops and under various clinical circumstances.

Tyrosine nitration of prostacyclin synthase is associated with enhanced retinal cell apoptosis in diabetes.

The risk of diabetic retinopathy is associated with the presence of both oxidative stress and toxic eicosanoids. Whether oxidative stress actually causes diabetic retinopathy via the generation of toxic eicosanoids, however, remains unknown. The aim of the present study was to determine whether tyrosine nitration of prostacyclin synthase (PGIS) contributes to retinal cell death in vitro and in vivo. Exposure of human retinal pericytes to heavily oxidized and glycated LDL (HOG-LDL), but not native forms of LDL (N-LDL), for 24 hours significantly increased pericyte apoptosis, accompanied by increased tyrosine nitration of PGIS and decreased PGIS activity. Inhibition of the thromboxane receptor or cyclooxygenase-2 dramatically attenuated HOG-LDL-induced apoptosis without restoring PGIS activity. Administration of superoxide dismutase (to scavenge superoxide anions) or L-N(G)-nitroarginine methyl ester (L-NAME, a nonselective nitric oxide synthase inhibitor) restored PGIS activity and attenuated pericyte apoptosis. In Akita mouse retinas, diabetes increased intraretinal levels of oxidized LDL and glycated LDL, induced PGIS nitration, enhanced apoptotic cell death, and impaired blood-retinal barrier function. Chronic administration of tempol, a superoxide scavenger, reduced intraretinal oxidized LDL and glycated LDL levels, PGIS nitration, and retina cell apoptosis, thereby preserving the integrity of blood-retinal barriers. In conclusion, oxidized LDL-mediated PGIS nitration and associated thromboxane receptor stimulation might be important in the initiation and progression of diabetic retinopathy.

Quantitative Measurements of Vessel Density and Blood Flow Areas Primary Angle Closure Diseases: A Study of Optical Coherence Tomography Angiography.

(1) Purpose: To measure the change in vessel density (VD) and the flow area (FA) on the retina of eyes with primary angle-closure diseases (PACD), including primary angle-closure suspect (PACS), primary angle-closure (PAC), acute primary angle-closure (APAC) and primary angle-closure glaucoma (PACG). (2) Methods: Patients with PACD were prospectively enrolled in this study. All participants underwent thorough ophthalmic examinations. The mean defect (MD), retinal nerve fiber layer (RNFL), ganglion cell complex (GCC) thickness, VD measurement, and blood FA were measured. (3) Results: A total of 147 eyes from 121 subjects were included in this study. The VD of the nerve head layer was significantly lower in PACG and APAC (all p < 0.001). APAC and PACG had lower FA of all layers, except for the choroid layer (p < 0.05). The macular VD of the whole image and blood FA in the superficial layer was significantly lower in PACG (all p < 0.001). The MD, RNFL, and GCC thickness demonstrated a strong correlation with whole image VD in the superficial layer (p < 0.001), while the inside disc VD did not show a significant correlation with MD, RNFL, and GCC thickness (p > 0.05). (4) Conclusions: There was a significant decrease in the VD and FA on the optic disc as well as the VD and FA of the superficial layer in the macular area in APAC and PACG. The changes in VD and FA are correlated with the severity of the glaucomatous structural damage and functional impairment.

Role of microglia autophagy and mitophagy in age-related neurodegenerative diseases.

Microglia, characterized by responding to damage, regulating the secretion of soluble inflammatory mediators, and engulfing specific segments in the central nervous system (CNS), function as key immune cells in the CNS. Emerging evidence suggests that microglia coordinate the inflammatory responses in CNS system and play a pivotal role in the pathogenesis of age-related neurodegenerative diseases (NDDs). Remarkably, microglia autophagy participates in the regulation of subcellular substances, which includes the degradation of misfolded proteins and other harmful constituents produced by neurons. Therefore, microglia autophagy regulates neuronal homeostasis maintenance and process of neuroinflammation. In this review, we aimed at highlighting the pivotal role of microglia autophagy in the pathogenesis of age-related NDDs. Besides the mechanistic process and the co-interaction between microglia autophagy and different kinds of NDDs, we also emphasized potential therapeutic agents and approaches that could be utilized at the onset and progression of these diseases through modulating microglia autophagy, including promising nanomedicines. Our review provides a valuable reference for subsequent studies focusing on treatments of neurodegenerative disorders. The exploration of microglia autophagy and the development of nanomedicines greatly enhances current understanding of NDDs.