Effect of topically applied 0.1% dexamethasone on endothelial healing and aqueous composition during the repair process of rabbit corneal alkali wounds

Chung, Jee Hyeok; Paek, Soo Min; Choi, Jung Jin; Park, Yoo Kyung; Lee, Jin Sung; Kim, Won Ki

doi:10.1076/ceyr.18.2.110.5375

Cited by 17 publications

(7 citation statements)

References 25 publications

(37 reference statements)

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“…Hence, we chose to use dexamethasone and doxycycline, which have been earlier studied and shown to reduce injury symptoms by the vesicating agents, NM and SM (Amir et al ., 2000; Banin et al ., 2003; Kadar et al ., 2009; Gordon et al ., 2010). Dexamethasone is an approved drug used to treat corneal burns and is reported to exert immunosuppressive and anti-inflammatory effects (Chung et al ., 1999; Kimura et al ., 2011) and doxycycline is a tetracycline derivative that is a broad-spectrum antibiotic can chelate metal ions, and has the ability to inhibit MMPs and synthesis of MMPs and IL-1(Solomon et al ., 2000; Smith and Cook, 2004). The studies herein demonstrate that treatments combining doxycycline and dexamethasone were more effective than doxycycline or dexamethasone alone in reversing most of the NM-induced injury markers such as epithelial thickness, microbullae formation, apoptotic cell death, and MMP-9 levels.…”

Section: Discussionmentioning

confidence: 99%

Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

Tewari‐Singh

Jain

Inturi

et al. 2012

Toxicology and Applied Pharmacology

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There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 µg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants.

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Section: Discussionmentioning

confidence: 99%

Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

Tewari‐Singh

Jain

Inturi

et al. 2012

Toxicology and Applied Pharmacology

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“…The healing rates were calculated by using linear regression analysis. 31 The culture medium was exchanged every day after the photographic procedure.…”

Section: In Vitro Experiments and Morphometrymentioning

confidence: 99%

Optimal concentration of human epidermal growth factor (hEGF) for epithelial healing in experimental corneal alkali wounds

Kim¹,

Jun²,

Kim³

et al. 2001

Current Eye Research

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“…B) and has been extensively used as an immunosuppressant and anti‐inflammatory agent . It is already approved for treatment of corneal burns, and it exerts anti‐inflammatory and immunosuppressive effects . Early application of dexamethasone has been shown to reduce the inflammatory response in SM‐induced injury .…”

Section: Treatment Of Vesicant‐induced Ocular Injuriesmentioning

confidence: 99%

“…73 It is already approved for treatment of corneal burns, and it exerts anti-inflammatory and immunosuppressive effects. 73,74 Early application of dexamethasone has been shown to reduce the inflammatory response in SM-induced injury. 12,36,75,76 Although prolonged use of dexamethasone is known to have some adverse side effects, except for a slight delay in corneal erosion healing, it is known to be quite well tolerated, without any clinical consequences.…”

Section: Dexamethasonementioning

confidence: 99%

Corneal toxicity induced by vesicating agents and effective treatment options

Goswami

Tewari‐Singh

Agarwal

2016

Annals of the New York Academy of Sciences

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The vesicating agents sulfur mustard (SM) and lewisite (LEW) are potent chemical warfare agents that primarily cause damage to the ocular, skin, and respiratory systems. However, ocular tissue is the most sensitive organ, and vesicant exposure results in a biphasic injury response, including photophobia, corneal lesions, corneal edema, ulceration, and neovascularization, and may cause loss of vision. There are several reports on ocular injury from exposure to SM, which has been frequently used in warfare. However, there are very few reports on ocular injury by LEW, which indicate that injury symptoms appear instantly after exposure and faster than SM. In spite of extensive research efforts, effective therapies for vesicant-induced ocular injuries, mainly to the most affected corneal tissue, are not available. Hence, we have established primary human corneal epithelial (HCE) cells and rabbit corneal organ culture models with the SM analog nitrogen mustard (NM), which have helped to test the efficacy of potential therapeutic agents. These agents will then be further evaluated against in vivo SM- and LEW-induced corneal injury models, which will assist in the development of potential broad-spectrum therapies against vesicant-induced ocular injuries.

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Effect of topically applied 0.1% dexamethasone on endothelial healing and aqueous composition during the repair process of rabbit corneal alkali wounds

Abstract: The present data indicate that dexamethasone may have a therapeutic potential in the management of endothelial healing after corneal alkali injury.

Cited by 17 publications

References 25 publications

Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

Optimal concentration of human epidermal growth factor (hEGF) for epithelial healing in experimental corneal alkali wounds

Corneal toxicity induced by vesicating agents and effective treatment options

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