Human amniotic epithelial cell-derived extracellular vesicles provide an extracellular matrix-based microenvironment for corneal injury repair.

To study the biological functions and applications of human amniotic epithelial cell-derived extracellular vesicles (hAEC-EVs), the cargos of hAEC-EVs were analyzed using miRNA sequencing and proteomics analysis. The hAECs and hAEC-EVs in this study had specific characteristics. Multi-omics analyses showed that extracellular matrix (ECM) reorganization, inhibition of excessive myofibroblasts, and promotion of target cell adhesion to the ECM were their primary functions. We evaluated the application of hAEC-EVs for corneal alkali burn healing in rabbits and elucidated the fundamental mechanisms. Slit-lamp images revealed that corneal alkali burns induced central epithelial loss, stromal haze, iris, and pupil obscurity in rabbits. Slit-lamp examination and histological findings indicated that hAEC-EVs facilitated re-epithelialization of the cornea after alkali burns, reduced scar formation and promoted the restoration of corneal tissue transparency. Significantly fewer α-SMA-positive myofibroblasts were observed in the hAEC-EV-treated group than the PBS group. HAEC-EVs effectively promoted the proliferation and migration of hCECs and hCSCs in vitro and activated the focal adhesion signaling pathway. We demonstrated that hAEC-EVs were excellent cell-free candidates for the treatment of ECM lesion-based diseases, including corneal alkali burns. HAEC-EVs promoted ECM reorganization and cell adhesion of target tissues or cells via orderly activation of the focal adhesion signaling pathway.

Small-Molecule Induction Promotes Corneal Endothelial Cell Differentiation From Human iPS Cells.

Purpose: Corneal endothelial cells (CECs) serve as a barrier and foothold for the corneal stroma to maintain the function and transparency of the cornea. Loss of CECs during aging or disease states leads to blindness, and cell replacement therapy using either donated or artificially differentiated CECs remains the only curative approach. Methods: Human induced pluripotent stem cells (hiPSCs) that were cultured in chemically defined medium were induced with dual-SMAD inhibition to differentiate into neural crest cells (NCCs). A small-molecule library was screened to differentiate the NCCs into corneal endothelial-like cells. The characteristics of these cells were identified with real-time PCR and immunofluorescence. Western blotting was applied to detect the signaling pathways and key factors regulated by the small molecules. Results: We developed an effective protocol to differentiate hiPSCs into CECs with defined small molecules. The hiPSC-CECs were characterized by ZO-1, AQP1, Vimentin and Na+/K+-ATPase. Based on our small-molecule screen, we identified a small-molecule combination, A769662 and AT13148, that enabled the most efficient production of CECs. The combination of A769662 and AT13148 upregulated the PKA/AKT signaling pathway, FOXO1 and PITX2 to promote the conversion of NCCs to CECs. Conclusion: We established an efficient small molecule-based method to differentiate hiPSCs into corneal endothelial-like cells, which might facilitate drug discovery and the development of cell-based therapies for corneal diseases.

Influences of personality characteristics and coping modes on anxiety in primary glaucoma patients.

AIM: To examine the influences of personality characteristics and coping modes on the anxiety of primary glaucoma patients. METHODS: A total of 200 individuals, including 50 with primary angle-closure glaucoma, 60 with primary open angle glaucoma and 90 control participants, filled out the State-Trait Anxiety Inventory, NEO Five-Factor Inventory, and Medical Coping Modes Questionnaire. Sociodemographic information was also collected. Data were analyzed via the Spearman rank correlation test and stepwise regression. RESULTS: The personality and coping variables are predictive and jointly account for a significant amount (45.3%-54.2%) of variance across the two subscales of anxiety measures. Notably, neuroticism seems to be most closely related to anxiety disturbances in glaucoma patients. The level of resignation is positively linked to anxiety scores. CONCLUSION: Some personality factors and coping modes help to predict the process of anxiety disorders in primary glaucoma patients. Recognizing the predictive role of these variables in the patients may further enrich clinical research in glaucoma and help to design more effective interventions involving both ophthalmology and psychiatry.

The 100 most influential papers about cataract surgery: a bibliometric analysis.

AIM: To identify the 100 most cited papers in cataract surgery, we performed a comprehensive bibliometric analysis basing on the literature search on the Thomson Reuters Web of Knowledge. METHODS: The number of citations, including the total citations, latest 5y citations and average citation number per year (ACY), authorship, year of publication, major topics, journal of publication, country and institution of origin of each paper were recorded and then analyzed. Pearson's correlation analysis was conducted to evaluate the correlation between the published year and the number of citations. The correlation between journal's impact factor (IF) and number of citations was assessed as well. RESULTS: The most cited paper was the classic paper done by the European Society of Cataract & Refractive Surgeons (ESCRS) group. This paper focused on the topic of endophthalmitis. Not only the most cited papers originated from the USA, but also some American institutions like Johns Hopkins University, Harvard Medical School, etc. had the most citations. Pearson's correlation analysis indicated that the latest 5y citations and ACY were significantly related with the published year (5y citations: r=0.615, P<0.001; ACY: r=0.657, P<0.001), whereas no association between the total number of citations and published year was found (r=0.045). Moreover, the IFs of journals were found to have no significant effect on the number of total citations. CONCLUSION: To our knowledge, this is the first study on the most influential papers in cataract surgery after a comprehensive research of relevant literatures. The present work may provide us concise information concerning the development history of cataract surgery over the past 66y.

Characteristics of corneal dystrophies: a review from clinical, histological and genetic perspectives.

Corneal dystrophy is a common type of hereditary corneal diseases. It includes many types, which have varied pathology, histology and clinical manifestations. Recently, the examination techniques of ophthalmology and gene sequencing advance greatly, which do benefit to our understanding of these diseases. However, many aspects remain still unknown. And due to the poor knowledge of these diseases, the results of the treatments are not satisfoctory. The purpose of this review was to summarize the clinical, histological and genetic characteristics of different types of corneal dystrophies.

Time-dependent matrix metalloproteinases and tissue inhibitor of metalloproteinases expression change in fusarium solani keratitis.

AIM: To investigate matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) expression during the progress of fusarium solani (F.solani) keratitis in a rat model. METHODS: A rat model of F.solani keratitis was produced using corneal scarification and a hand-made contact lens. MMPs and TIMPs expressiond were explored in this rat model of F.solani keratitis using real-time polymerase chain reaction (PCR) and DIF. GM6001 (400 µmol/mL) was used to treat infected corneas. The keratitis duration, amount and area of corneal neovascularization (CNV) were evaluated. RESULTS: MMP-3 expression was 66.3 times higher in infected corneas compared to normal corneas. MMP-8, -9, and -13 expressions were significantly upregulated in the mid-period of the infection, with infected-to-normal ratios of 4.03, 39.86, and 5.94, respectively. MMP-2 and -7 expressions increased in the late period, with the infected-to-normal ratios of 5.94 and 16.22, respectively. TIMP-1 expression was upregulated in the early period, and it was 43.17 times higher in infected compared to normal corneas, but TIMP-2, -3, and -4 expressions were mildly downregulated or unchanged. The results of DIF were consistent with the result of real-time PCR. GM6001, a MMPs inhibitor, decreased the duration of F.solani infection and the amount and area of CNV. CONCLUSION: MMPs and TIMPs contributed into the progress of F.solani keratitis.

Femtosecond laser in refractive and cataract surgeries.

In the past few years, 9 unique laser platforms have been brought to the market. As femtosecond (FS) laser-assisted ophthalmic surgery potentially improves patient safety and visual outcomes, this new technology indeed provides ophthalmologists a reliable new option. But this new technology also poses a range of new clinical and financial challenges for surgeons. We provide an overview of the evolution of FS laser technology for use in refractive and cataract surgeries. This review describes the available laser platforms and mainly focuses on discussing the development of ophthalmic surgery technologies.

Bone marrow mesenchymal stem cells protect against retinal ganglion cell loss in aged rats with glaucoma.

Glaucoma is a common eye disease in the aged population and has severe consequences. The present study examined the therapeutic effects of bone marrow mesenchymal stem cell (BMSC) transplantation in preventing loss of visual function in aged rats with glaucoma caused by laser-induced ocular hypertension. We found that BMSCs promoted survival of retinal ganglion cells in the transplanted eye as compared with the control eye. Further, in swimming tests guided by visual cues, the rats with a BMSC transplant performed significantly better. We believe that BMSC transplantation therapy is effective in treating aged rats with glaucoma.

[Seroepidemiological survey of chickens infected with Toxoplasma gondii in Wuxi City].

OBJECTIVE: To understand the status of scattered chickens infected with Toxoplasma gondii in Wuxi City. METHODS: We investigated the positive rate of Toxoplasma antigen and antibody of 309 cases of scattered chickens in Wuxi, and it was compared with the positive rate of Toxoplasma antigen and antibody of 150 cases of intensive farming chickens. RESULTS: In the 309 cases of scattered chickens, there were 29 cases of antigen positive, and the positive rate was 9.39%; there were 53 cases of antibody positive, and the positive rate was 17.15%; there were 13 cases of antigen and antibody double positive, and the double-positive rate was 4.21%.; In the scattered chickens, the overall positive rate was 22.33%, and in the intensive farming chickens, the overall positive rate was 2.67%, and there was a significant difference between them (chi2 = 29.19, P <0.01). CONCLUSION: There is a high T. gondii infection in scattered chickens in Wuxi, so the medical, veterinary and food hygiene workers should pay more attention to it.

[Risk factors of primary angle closure glaucoma].

Primary angle closure glaucoma is one of the common diseases causing blindness. The pathogenesis inducing primary angle closure glaucoma has not been entirely clear. Traditionally identified risk factors include shallow anterior chamber, short axial length and thicker lens. Recent studies begin to pay attention to other new risk factors, not only including static anatomical factors, such as anterior chamber volume, iris curvature and lens vault, but also including dynamic changing factors, such as dynamic dilation of iris volume and choroidal effusion. Comprehensive assessment of these risk factors is of great significance for early diagnosis and treatment of angle closure glaucoma. This article briefly reviews research advances in risk factors of primary angle closure glaucoma.

Experimental model of Fusarium solani keratitis in rats.

AIM: To establish a repeatable rat model of Fusarium solani keratitis (F. solani keratitis) that mimicked fungal keratitis in humans. METHODS: Wistar rats' corneas were scratched on the superficial stroma after scraping the unilateral corneal epithelia. Then, the corneal surface was inoculated with different inoculum dose of F. solani spore suspension. Doses ranged from 10(6) to 10(9) colony-forming unit per milliliter (CFU/mL). The treated corneas were covered by contact lenses that were made of Parafilm M membrane. Negative controls were inoculated with sterile phosphate-buffered saline (PBS). For statistical analysis, corneas were evaluated daily on a 12-point scale to check the state of corneal inflammation. Furthermore, the pathological characteristics of this model were investigated. RESULTS: The rat model of F. solani keratitis was established by the combination methods of corneal trauma and parafilm-made contact lens and inoculation of fungus spore suspension. 10(6) and 10(7)CFU/mL of F. solani induced mild corneal infection, while 10(8)CFU/mL of F. solani was sufficient to induce moderate infection that was consistent with human keratomycosis. Dose of 10(9)CFU/mL of F. solani was excessive and led to perforated corneas. CONCLUSION: The rat model of F. solani keratitis, established by the combinational methods of corneal trauma, parafilm-made contact lens and the appropriate dose of inoculum, that imitates the developing processes of F. solani keratitis in human beings and provides a repeatable method of creating a rat model.