establishment-of-a-mouse-model-of-aqueous-deficiency-dry-eye

Establishment of A Mouse Model of Aqueous Deficiency Dry Eye

Dry eye disease is a prevalent condition affecting 5%-50% of the global population. Animal model investigations play a crucial role in understanding its ...

the Affiliated Hospital of Guizhou Medical University

Guizhou Medical University

The aim of the study was to review the distribution, current trends, and microbiological characteristics of bacterial pathogens isolated from dacryocystitis patients in China during the last 15 years.This is a retrospective multiple-center noncomparative case series. The medical records of 15,452 consecutive patients from 7 cities diagnosed as having dacryocystitis between 2002 and 2016 were reviewed. The patients' demographics, microbiological data, and antibiotic sensitivity were reviewed and analyzed.A total of 3344 lacrimal sac content cultures were taken (21.6%) during the study period. A pathogen was identified in 1996 samples (59.7%), with bacterial isolates accounting for 1902 of the positive cultures (95.3%). Gram-positive isolates, gram-negative isolates, and anaerobic bacteria were found in 1218 (61.0%), 607 (30.4%), and 285 (14.3%) samples, respectively. An increase in gram-positive isolates over the study duration was found (P = .003). The predominant isolates were coagulase negative Staphylococci (485, 25.5%), Staphylococcus aureus (186, 9.8%), Pseudomonas aeruginosa (184, 9.7%), and Haemophilus influenzae (152, 9.0%). There was a trend toward increasing resistance to erythromycin from 10.5% during the first 5 years of the study to 20.7% during the last 5 years (P < .001). Antimicrobial susceptibility testing showed that gatifloxacin was the most effective drug against most of gram-positive, gram-negative, and anaerobic bacteria.The microbial culture rate of dacryocystitis in China is low. There was an increase in the percentage of gram-positive bacteria over time. The sensitivity of gram-positive isolates to tested antibiotics is relatively low compared with that of gram-negative isolates. Our data show that the empiric use of fourth-generation fluoroquinolones in refractory dacryocystitis may be justified.

Trends in dacryocystitis in China: A STROBE-compliant article.

To characterize the accommodative changes in high-myopic patients after the implantation of the Visian implantable collamer lens with a central hole (ICL V4c).This prospective study enrolled 30 patients (60 eyes) with uneventful surgery of ICL V4c implantation. Parameters including amplitude of accommodation (AA), monocular and binocular facility of accommodation (FA), positive relative accommodation (PRA), negative relative accommodation (NRA), near point convergence (NPC), accommodative response, and accommodation convergence/accommodation (AC/A) ratio were assessed before surgery, at 1 and 3 months postoperatively.Mean preoperative SE was -10.86 ± 3.87 diopter (D) (range, -6.5D to -22D), which improved to 0.27 ± 0.51D at 1 month and 0.09 ± 0.47D at 3 months after surgery (P <.001). Significant improvements in AA, NRA, PRA, NPC, monocular, and binocular FA were seen at 1 month and 3 months postoperatively compared to the values before surgery (P <.05), but the difference between 1 month and 3 months were not obvious (P >.05) except for binocular FA (P = .002). However, no significant changes were seen in either AC/A ratio or accommodative response at any postoperative follow-ups in contrast to those before surgery (P >.05). Similar changes in accommodative function were found in patients with less myopia (> -10.00D) and those with more myopia (≤10.00D) (P >.05).The accommodative function of eyes after the implantation of ICL V4c is enhanced and stabilizes at 1 month, except for the AC/A ratio and accommodative response. The clearer vision and increased amount of accommodation for near target account for the majority of the improvement.

Accommodation changes after visian implantable collamer lens with central hole for high myopia: A STROBE-compliant article.

To demonstrate the identification of corneal diseases using a novel deep learning algorithm. A novel hierarchical deep learning network, which is composed of a family of multi-task multi-label learning classifiers representing different levels of eye diseases derived from a predefined hierarchical eye disease taxonomy was designed. Next, we proposed a multi-level eye disease-guided loss function to learn the fine-grained variability of eye diseases features. The proposed algorithm was trained end-to-end directly using 5,325 ocular surface images from a retrospective dataset. Finally, the algorithm's performance was tested against 10 ophthalmologists in a prospective clinic-based dataset with 510 outpatients newly enrolled with diseases of infectious keratitis, non-infectious keratitis, corneal dystrophy or degeneration, and corneal neoplasm. The area under the ROC curve of the algorithm for each corneal disease type was over 0.910 and in general it had sensitivity and specificity similar to or better than the average values of all ophthalmologists. Confusion matrices revealed similarities in misclassification between human experts and the algorithm. In addition, our algorithm outperformed over all four previous reported methods in identified corneal diseases. The proposed algorithm may be useful for computer-assisted corneal disease diagnosis.

Deep learning for identifying corneal diseases from ocular surface slit-lamp photographs.

 To elucidate the expression profile and the potential role of long non-coding ribonucleic acids (RNAs) (lncRNAs) in a dry eye disease (DED) model.  A DED model was established in C57BL/6J mice with 0.2% benzalkonium chloride (BAC) twice a day for 14 days. The differentially expressed lncRNAs were detected by RNA-seq technology (Gene Expression Omnibus, GEO GSE186450) and the aberrantly expressed lncRNAs were further verified by RT-qPCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to predicate the related candidate genes and potential pathological pathways. Cells from a human corneal epithelial cell line (HCECs) were cultured under hyperosmolarity. The regulation of inflammatory factors by silencing potential targeted lncRNAs was verified  in HCECs.  In our study, a significant increase in corneal fluorescence staining and a reduction in tear production were observed in DED mice at all follow-ups compared with the controls, and the differences were increasing over time. In total, 2,649 upregulated and 704 downregulated lncRNAs were identified in DED mice. We selected six aberrantly expressed and most abundant lncRNAs and performed RT-qPCR using the samples for RNA-seq. Chrnb2, Gabarapl2, and Usp31 were thereby confirmed as the most significantly altered lncRNAs. Pathway analysis revealed that the neuroactive ligand-receptor interaction signaling pathway was the most enriched, followed by the calcium signaling pathway and cytokine-cytokine receptor interaction. Following treatment of Gabarapl2 siRNA and Chrnb2 siRNA, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were significantly downregulated in the HCECs.  Our study suggests that Chrnb2 and Gabarapl2 may be involved in the inflammation response by regulating TNF-α, IL-1β, and IL-6 in DED. These candidate lncRNAs may be both potential biomarkers and therapeutic targets for DED.

Long Non-coding RNAs Gabarapl2 and Chrnb2 Positively Regulate Inflammatory Signaling in a Mouse Model of Dry Eye.

Enhancer RNAs (eRNAs) have emerged as key players in the pathology of several tumors, including uveal melanoma. Here, we aimed to explore the prognostic values of eRNAs in uveal melanoma (UVM) patients. The expressing data and survival data of UVM patients were downloaded from TCGA and GSE22138 datasets. The Kaplan-Meier methods with the log-rank test were applied to screen survival-related eRNAs in UVM. GEPIA was applied to analyze the associations between expressions of eRNA and disease-free survival. KEGG assays were applied to explore the potential signaling pathways of the key eRNA. The prognostic values of eRNAs were further explored by multivariate assays by the R package survival. The eRNAs were validated in pan-cancer. In this study, we identified 89 survival-related eRNAs in UVM based on TCGA datasets. Based on GSE22138 datasets, we found 27 survival-related eRNAs in UVM. Only two eRNAs (LINC00689 and ELFN1-AS1) were overlapped in both two datasets. The results of multivariate analysis revealed that both LINC00689 and ELFN1-AS1 were independent prognostic factors in UVM patients. The pan-cancer validation results further confirmed the prognostic values of LINC00689 and ELFN1-AS1 in eight tumors. Overall, we identified two novel UVM-related eRNAs, LINC00689 and ELFN1-AS1 which may serve as prognostic and diagnostic biomarkers of UVM patients for clinical decision-making.

Comprehensive Analysis of Enhancer RNAs Identifies LINC00689 and ELFN1-AS1 as Novel Prognostic Biomarkers in Uveal Melanoma.

Allergic conjunctivitis (AC) is one of the most common ocular disorders in clinical practice and is associated with meibomian gland dysfunction. This study aimed to explore the morphological and functional changes of meibomian glands (MGs) in pediatric and adult patients with AC and to analyze their potential predictors. In our prospective, observational cohort study, a total of 59 patients with AC were enrolled, with 30 patients aged ≤16 years in the pediatric group and 29 patients in the adult group. All patients underwent examinations at baseline and last visit when the complete resolution of conjunctival papillae was identified. An automatic MG analyzer was used to measure the morphological and functional parameters of MGs, including their area ratio (GA), tortuosity index (TI), and signal index (SI). Two groups were comparable at baseline in terms of characteristics and MG parameters (p > 0.05). The morphological (length, square, and GA) and functional MG parameters (SI) of AC patients significantly improved in the pediatric group after treatment (all p < 0.05), but not in the adult group. The change in the GA correlated with age, sex, GA, TI, and SI at baseline (all p < 0.05). Age (p = 0.001) and GA (p < 0.001) at baseline were predictors of an improvement in the GA of MGs. The findings showed that the structure and function of MGs in pediatric patients with AC seem to improve after the conjunctival papillae disappear, but not in adult patients.

Morphological and Functional Changes of Meibomian Glands in Pediatric and Adult Patients with Allergic Conjunctivitis.

Increasing studies have identified the function of sirtuin-1 (SIRT1) in ocular diseases. Hence, this study is aimed at exploring the potential role of SIRT1 in choroidal neovascularization- (CNV-) induced age-related macular degeneration (AMD) development and the associated mechanism. Expression of SIRT1/SOX9/LCN2 in the hypoxic cells was determined, and their interactions were predicted by bioinformatics websites and followed by the verification by luciferase assay and chromatin immunoprecipitation (ChIP). Their  effects on hypoxic cells concerning cell viability, apoptosis, migration, and angiogenesis were detected through gain- and loss-of-function assays. Besides, their  effect was explored using the established CNV mouse models. Highly expressed LCN2, SOX9, and SIRT1 were observed in hypoxic cells. LCN2 was increased by SOX9 and SIRT1 deacetylated SOX9 to promote its nuclear translocation, which further inhibited the viability of human retinal pigment epithelial cells and promoted cell apoptosis and angiogenesis as well as CNV-induced AMD formation. The relieving role of LCN2 inhibition on CNV-induced AMD without toxicity for mice was also demonstrated by  experiments. Overall, SIRT1 promoted the formation of CNV-induced AMD through SOX9 deacetylation-caused LCN2 upregulation, representing a promising target for CNV-induced AMD management.

Sirtuin 1 Induces Choroidal Neovascularization and Triggers Age-Related Macular Degeneration by Promoting LCN2 through SOX9 Deacetylation.

To evaluate the efficacy and safety of eyelid hygiene using topical 0.01% hypochlorous acid (HOCL) through ultrasonic atomization after 2 weeks in patients with blepharitis.

Effect of Hypochlorous Acid on Blepharitis through Ultrasonic Atomization: A Randomized Clinical Trial.

Dry eye disease (DED) is a prevalent eye disorder. Cyclosporine is an effective immunomodulator that is widely used in DED; however, due to its highly hydrophobic nature, delivery of cyclosporine to the ocular surface is challenging.

Water-Free Cyclosporine Ophthalmic Solution vs Vehicle for Dry Eye Disease: A Randomized Clinical Trial.

Currently, in vitro cultured corneal epithelial transplantation is effective in treating limbal stem cell dysfunction (LSCD). Selecting carriers is crucial for constructing the corneal epithelium through tissue engineering. In this study, the traditional amniotic membrane (AM) was modified, and mesenchymal stem cells (MSCs) were inoculated into the ultra-thin amniotic membrane (UAM) stroma to construct a novel UAM-MSC tissue-engineered corneal epithelial carrier, that could effectively simulate the limbal stem cells (LSCs) microenvironment. The structure of different carriers cultured tissue-engineered corneal epithelium and the managed rabbit LSCD model corneas were observed through hematoxylin-eosin staining. Cell phenotypes were evaluated through fluorescence staining, Western blotting, and RT-qPCR. Additionally, cell junction genes and expression markers related to anti-neovascularization were evaluated using RT-qPCR. Corneal epithelium cell junctions were observed via an electron microscope. The tissue-engineered corneal epithelium culture medium was analyzed through mass spectrometry. Tissue-engineered corneal epithelial cells expanded by LSCs on UAM-MSCs had good transparency. Simultaneously, progenitor cell (K14, PNCA, p63) and corneal epithelial (PAX6) gene expression in tissue-engineered corneal epithelium constructed using UAM-MSCs was higher than that in corneal epithelial cells amplified by UAM and de-epithelialized amniotic membrane. Electron microscopy revealed that corneal epithelial cells grafted with UAM-MSCs were closely connected. In conclusion, the UAM-MSCs vector we constructed could better simulate the limbal microenvironment; the cultured tissue-engineered corneal epithelium had better transparency, anti-neovascularization properties, closer intercellular connections, and closer resemblance to the natural corneal epithelial tissue phenotype.

A novel tissue-engineered corneal epithelium based on ultra-thin amniotic membrane and mesenchymal stem cells.

Fuchs endothelial corneal dystrophy (FECD) stands as the most prevalent primary corneal endothelial dystrophy worldwide, posing a significant risk to corneal homeostasis and clarity. Corneal endothelial cells exhibit susceptibility to oxidative stress, suggesting a nuanced relationship between oxidant-antioxidant imbalance and FECD pathogenesis, irrespective of FECD genotype. Given the constrained availability of corneal transplants, exploration into non-surgical interventions becomes crucial. This encompasses traditional antioxidants, small molecule compounds, biologics, and diverse non-drug therapies, such as gene-related therapy, hydrogen therapy and near infrared light therapy. This review concentrates on elucidating the mechanisms behind oxidant-antioxidant imbalance and the evolution of strategies to restore oxidant-antioxidant balance in FECD. It provides a comprehensive overview of both conventional and emerging therapeutic approaches, offering valuable insights for the advancement of non-surgical treatment modalities. The findings herein might establish a robust foundation for future research and the therapeutic strategy of FECD.

Hao Gu

Department of Ophthalmology

the Affiliated Hospital of Guizhou Medical University

Establishment of A Mouse Model of Aqueous Deficiency Dry Eye

Hao Gu

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Ophthalmology

the Affiliated Hospital of Guizhou Medical University

Establishment of A Mouse Model of Aqueous Deficiency Dry Eye

Department of Ophthalmology