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

Oxidative stress may cause ocular surface damage during the development of dry eye. Mammalian cells have defense systems against oxidative stress. A central regulator of the stress response is nuclear factor-erythroid 2-related factor 2 (NFE2L2). NFE2L2 is activated by the novel triterpenoid RS9 (a biotransformation compound of RTA 402). The purpose of this study was to assess the efficacy of RS9 against dry eye using in vitro and in vivo models. Bioactivity was estimated by the induction of mRNAs for two NFE2L2-targeted genes: NQO1 (prevents radical species) and GCLC (glutathione synthesis), using a corneal epithelial cell line (HCE-T). Protection against oxidation and cell damage was tested in vitro by culturing cells under hyperosmotic stress or by the addition of menadione, a generator of reactive oxygen species (ROS). Dry eye in vivo was induced by the injection of scopolamine into rats. Then, 930 nM of RS9 was applied to both eyes for 2 weeks. Oxidative stress was measured by the accumulation of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Corneal wound healing was measured by scoring for superficial punctate keratitis (SPK). Corneal epithelial cell densities were evaluated histologically. RS9 and RTA 402 induced the expression of NQO1 and GCLC mRNAs in HCE-T cells. And both compounds suppressed hyperosmotic-ROS generation and menadione induced cellular damage. However RS9 had a stronger protective effect than RTA 402. Ocular instillation of RS9 also significantly upregulated the expression of Nqo1 mRNA in the corneal epithelium. Accumulation of 8-OHdG, increase of SPK scores and decrement of basal cell density were observed in corneal epithelium from scopolamine-injected rats. These changes were significantly ameliorated by the topical administration of RS9. RS9 induced Nfe2l2 activation and Nfe2l2-targeted genes, reduced oxidation, and ameliorated symptoms of dry eye using in vitro and in vivo models. Thus, RS9 might be a potent candidate agent against dry eye disease.
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PMID:NFE2L2 activator RS9 protects against corneal epithelial cell damage in dry eye models. 3232 Apr 33

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.
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PMID:Esculetin protects human corneal epithelial cells from oxidative stress through Nrf-2 signaling pathway. 3322 Feb 36