Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0314719 (dry eye)
 2,625 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The corneal epithelium exists at the surface of cornea and is easily damaged by external stresses such as UV radiation or physical injury. The Nrf2-mediated defense system plays a central role in protecting cells by activating genes against these types of stress. In this study, we investigated the role of the Nrf2-mediated defense system in corneal epithelial wound healing by using Nrf2-knockout (KO) mice. Nrf2 was expressed in the corneal epithelium of wild-type (WT) mice, but not in KO mice. Observation of wounds after 24h of healing revealed that healing of the corneal epithelium was significantly delayed in the Nrf2 KO mice, whereas Nrf2 was activated in the corneal epithelium of WT mice. Ki-67 staining revealed that the number of Ki-67-positive proliferating cells was significantly lower in the Nrf2 KO mice than in the WT mice at 24-36h after injury; however, these numbers were approximately equivalent by 48h. To clarify the role of Nrf2 during wound healing, we performed in vitro experiments with siRNA for Nrf2 and its suppressor Keap1. Nrf2 knockdown significantly delayed corneal epithelial cell migration, but did not affect cell proliferation. Conversely, Keap1 knockdown significantly accelerated cell migration. These results suggest that Nrf2 contributed to the corneal epithelial wound-healing process by accelerating cell migration, and Nrf2 would therefore be a good target for the treatment of corneal epithelial diseases such as dry eye or chronic corneal epithelial defect.
...
PMID:The role of the Nrf2-mediated defense system in corneal epithelial wound healing. 2358 56

An increase in the osmolarity of tears induced by excessive evaporation of the aqueous tear phase is a major pathological mechanism behind dry eye. Exposure of epithelial cells on the surface of the human eye to hyperosmolarity leads to oxidative stress, mitochondrial dysfunction, and apoptosis. Edaravone, a hydroxyl radical scavenging agent, is clinically used to reduce neuronal damage following ischemic stroke. In this study, we found that treatment with hyperosmotic media at 400 and 450 mOsM increased the levels of ROS and mitochondrial oxidative damage, which were ameliorated by edaravone treatment in a dose-dependent manner. We also found that edaravone could improve mitochondrial function in HCEpiCs by increasing the levels of ATP and mitochondrial membrane potential. MTT and LDH assays indicated that edaravone could attenuate hyperosmolarity-induced cell death. It was found that edaravone prevented apoptosis by decreasing the level of cleaved caspase-3, and attenuating the release of cytochrome C. Mechanistically, we found that edaravone augmented the expression of Nrf2 and its target genes, such as HO-1, GPx-1, and GCLC.
 ...
PMID:Edaravone protects against hyperosmolarity-induced oxidative stress and apoptosis in primary human corneal epithelial cells. 2834 81

Dry eye formation often originates from oxidative damage to the ocular surface, which can be caused by external environment or internal pathologic factors. Esculetin (6, 7-dihydroxycoumarin) is a natural product found in many plants, and has been reported to have multiple pharmacological activities. The objective of our present study is to investigate if esculetin could protect the corneal epithelial cells from oxidative damages and its underlying antioxidant molecular mechanisms. Our experimental results demonstrated that pretreatment with esculetin markedly increased the cell viability while decreased the apoptosis in H2O2-treated human corneal epithelial (HCE) cells, by regulating Bcl-2, Bax and caspase-3 protein expressions and by altering the imbalance of activities of intracellular reactive oxygen species (ROS) and superoxide dismutase (SOD). Our data revealed that esculetin played an antioxidant role not only through its antioxidant activity, but also by highly inducing Nrf-2 translocation to the nucleus, which in turn, enhanced Nrf2 signaling regulated antioxidant genes (HO-1, NQO1, GCLM, SOD1 and SOD2) mRNA expression levels in H2O2-treated HCE cells. In the present study, the protective effects of esculetin on the corneal epithelium were also confirmed by a murine desiccating stress induced dry eye model in vivo. These data illustrated, for the first time, that esculetin may have the ability to protect human corneal epithelial cells from oxidative damages through its scavenging of free radical properties and through the activation of Nrf2 signaling.
 ...
PMID:Esculetin protects human corneal epithelial cells from oxidative stress through Nrf-2 signaling pathway. 3322 Feb 36