Presently, eye injuries are treated by topical eye drop therapy. Because of the ocular surface barriers, topical eye drops must be applied several times in a day, causing side effects such as glaucoma, cataract, and poor patient compliance. This article presents the development of a nanowafer drug delivery system in which the polymer and the drug work synergistically to elicit an enhanced therapeutic efficacy with negligible adverse immune responses. The nanowafer is a small transparent circular disc that contains arrays of drug-loaded nanoreservoirs. The slow drug release from the nanowafer increases the drug residence time on the ocular surface and its subsequent absorption into the surrounding ocular tissue. At the end of the stipulated period of drug release, the nanowafer will dissolve and fade away. The in vivo efficacy of the axitinib-loaded nanowafer was demonstrated in treating corneal neovascularization (CNV) in a murine ocular burn model. The laser scanning confocal imaging and RT-PCR study revealed that once a day administered axitinib nanowafer was therapeutically twice as effective, compared to axitinib delivered twice a day by topical eye drop therapy. The axitinib nanowafer is nontoxic and did not affect the wound healing and epithelial recovery of the ocular burn induced corneas. These results confirmed that drug release from the axitinib nanowafer is more effective in inhibiting CNV compared to the topical eye drop treatment even at a lower dosing frequency.
Purpose. To analyze the prevalence and presentation patterns of corneal astigmatism in cataract surgery candidates in a teaching hospital in northern China. Methods. From May 1, 2012, to April 30, 2013, partial coherence interferometry (IOLMaster) measurements of all qualified cataract surgery candidates were retrospectively collected and analyzed. Results. The study evaluated 12,449 eyes from 6,908 patients with a mean age of 69.80 ± 11.15 (SD) years. The corneal astigmatism was 0.5 diopters (D) or less in 20.76% of eyes, 1.0 D or more in 47.27% of eyes, 2.0 D or more in 13.16% of eyes, and 3.0 D or more in 3.75% of eyes. With-the-rule astigmatism was found in 30.36% of eyes, while against-the-rule was found in 52.41% of eyes. The percentage of against-the-rule astigmatism increased with age. Conclusion. Our study showed that almost one-half of preoperative eyes (47.27%) in northern China have a corneal astigmatism of 1.0 D or more, indicating that more surgical techniques or toric IOLs are needed to achieve better visual rehabilitation.
The concept of innate immunity has been expanded to recognize environmental pathogens other than microbial components. However, whether and how the innate immunity is initiated by epithelium in response to environmental physical challenges such as low humidity and high osmolarity in an autoimmune disease, dry eye, is still largely unknown. Using two experimental dry eye models, primary human corneal epithelial cultures exposed to hyperosmolarity and mouse ocular surface facing desiccating stress, we uncovered novel innate immunity pathway by ocular surface epithelium, where oxidized mitochondrial DNA induces imbalanced activation of NLRP3/NLRP6 inflammasomes via stimulation of caspase-8 and BRCC36 in response to environmental stress. Activated NLRP3 with suppressed NLRP6 stimulates caspase-1 activation that leads to IL-1β and IL-18 maturation and secretion. NLRP3-independent caspase-8 noncanonically activates caspase-1 via reciprocal regulation of NLRP3/NLRP6-mediated inflammasomes. Reactive oxygen species-induced mitochondrial DNA oxidative damage and BRCC36 deubiquitinating activity provide a missing link and mechanism by which innate immunity responds to environmental stress via caspase-8-involved NLRP3/NLRP6 inflammasomes.
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