Establishment of a 3D In Vitro Model to Accelerate the Development of Human Therapies against Corneal Diabetes

The authors thank Dr. John M Asara, Min Yuan, and Susanne Breitkopf for their technical help with metabolomics experiments, Dr. Ben Fowler for his technical help with TEM experiments and also Tina B McKay for many thoughtful discussions and scientific insights during the study.Purpose To establish an in vitro model that would mirror the in vivo corneal stromal environment in diabetes (DM) patients. Methods Human corneal fibroblasts from Healthy (HCFs), Type 1DM (T1DM) and Type 2DM (T2DM) donors were isolated and cultured for 4 weeks with Vitamin C stimulation in order to allow for extracellular matrix (ECM) secretion and assembly. Results Our data indicated altered cellular morphology, increased cellular migration, increased ECM assembly, and severe mitochondrial damage in both T1DM and T2DMs when compared to HCFs. Furthermore, we found significant downregulation of Collagen I and Collagen V expression in both T1DM and T2DMs. Furthermore, a significant up regulation of fibrotic markers was seen, including α-smooth muscle actin in T2DM and Collagen III in both T1DM and T2DMs. Metabolic analysis suggested impaired Glycolysis and Tricarboxylic acid cycle (TCA) pathway. Conclusion DM has significant effects on physiological and clinical aspects of the human cornea. The benefits in developing and fully characterizing our 3D in vitro model are enormous and might provide clues for the development of novel therapeutics.Yeshttp://www.plosone.org/static/editorial#pee

Change of Optical Intensity during Healing Process of Corneal Wound on Anterior Segment Optical Coherence Tomography

The purpose of this study is to investigate the process of corneal wound healing after penetrating injury with the change in optical intensity on anterior segment optical coherence tomography (AS-OCT) and to investigate factors associated with severity of corneal scar. Forty-seven eyes from 47 patients with repaired corneal laceration were included. AS-OCT was performed on 1day, 1week, 1, 3 and 6 months after primary repair. Internal aberrations of wound edges were observed on AS-OCT images. Parameters including height of steps, width of gaps, maximal corneal thickness, area and optical intensity of corneal wound/scar were measured. The relationship between the parameters at day 1 and the optical intensity at 6 months were analyzed. The results showed that optical intensity of corneal wound/scar increased from 124.1 ± 18.8 on day 1 postoperatively to 129.3 ± 18.7, 134.2 ± 23.4, 139.7 ± 26.5, 148.2 ± 26.4 at 1 week, 1 month, 3 months and 6 months postoperatively. Height of steps at 1 day after surgery was the only factor identified as correlated with optical intensity of corneal scar at 6 months (beta = 0.34, p = 0.024). The increase of optical intensity represents the process of fibrosis of corneal wound healing. Higher step after suturing is associated with more severity of corneal scar at last

Extracellular matrix assembly: a multiscale deconstruction

The biochemical and biophysical properties of the extracellular matrix (ECM) dictate tissue-specific cell behaviour. The molecules that are associated with the ECM of each tissue, including collagens, proteoglycans, laminins and fibronectin, and the manner in which they are assembled determine the structure and the organization of the resultant ECM. The product is a specific ECM signature that is comprised of unique compositional and topographical features that both reflect and facilitate the functional requirements of the tissue

Rivaroxaban with or without aspirin in stable cardiovascular disease

BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=−4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events