Beneficial effects of topical anti-inflammatory drugs against sulfur mustard-induced ocular lesions in rabbits

Amir, Adina; Turetz, J.; Chapman, Shira; Fishbeine, E.; Meshulam, Jeffrey; Sahar, Rita; Liani, H.; Gilat, Eran; Frishman, G.; Kadar, Tamar

doi:10.1002/1099-1263(200012)20:1+<::aid-jat669>3.0.co;2-7

Cited by 52 publications

(55 citation statements)

References 12 publications

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“…41 Our experiments showed this also, detecting neovascularization at 7 and 28 days time points. Interestingly, the hydrogel formulation appeared to reduce the amount of neovascularization, although this must be studied further considering the small number of animals tested.…”

supporting

confidence: 65%

Doxycycline Hydrogels as a Potential Therapy for Ocular Vesicant Injury

Gordon

Desantis

Deshmukh

et al. 2010

Journal of Ocular Pharmacology and Therapeutics

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Purpose: The goals of this study were (1) to compare the injury at the basement membrane zone (BMZ) of rabbit corneal organ cultures exposed to half mustard (2 chloroethyl ethyl sulfide, CEES) and nitrogen mustard with that of in vivo rabbit eyes exposed to sulfur mustard (SM); (2) to test the efficacy of 4 tetracycline derivatives in attenuating vesicant-induced BMZ disruption in the 24-h period postexposure; and (3) to use the most effective tetracycline derivative to compare the improvement of injury when the drug is delivered as drops or hydrogels to eyes exposed in vivo to SM. Methods: Histological analysis of hematoxylin and eosin-stained sections was performed; the ultrastructure of the corneal BMZ was evaluated by transmission electron microscopy; matrix metalloproteinase-9 was assessed by immunofluorescence; doxycycline as drops or a hydrogel was applied daily for 28 days to eyes exposed in vivo to SM. Corneal edema was assessed by pachymetry and the extent of neovascularization was graded by length of longest vessel in each quadrant. Results: Injury to the BMZ was highly similar with all vesicants, but varied in degree of severity. The effectiveness of the 4 drugs in retaining BMZ integrity did not correlate with their ability to attenuate matrix metalloproteinase-9 expression at the epithelial-stromal border. Doxycycline was most effective on organ cultures; therefore, it was applied as drops or a hydrogel to rabbit corneas exposed in vivo to SM. Eyes were examined at 1, 3, 7, and 28 days after exposure. At 7 and 28 days after SM exposure, eyes treated with doxycycline were greatly improved over those that received no therapy. Corneal thickness decreased somewhat faster using doxycycline drops, whereas the hydrogel formulation decreased the incidence of neovascularization. Conclusions: Corneal cultures exposed to 2-chloroethyl ethyl sulfide and nitrogen mustard were effective models to simulate in vivo SM exposures. Doxycycline as drops and hydrogels ameliorated vesicant injury. With in vivo exposed animals, the drops reduced edema faster than the hydrogels, but use of the hydrogels significantly reduced neovascularization. The data provide proof of principle that a hydrogel formulation of doxycycline as a daily therapy for ocular vesicant injury should be further investigated.

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supporting

confidence: 65%

Doxycycline Hydrogels as a Potential Therapy for Ocular Vesicant Injury

Gordon

Desantis

Deshmukh

et al. 2010

Journal of Ocular Pharmacology and Therapeutics

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“…We have already tested and reported recently the usefulness of this model for the evaluation of a potential therapy against these lesions. [25][26] The experimental model…”

Section: Discussionmentioning

confidence: 99%

“…It is clear that inflammation plays a key role in propagating the HD-delayed response, since anti-inflammatory treatment decreased the primary inflammatory reaction as well as the extent of NV. [25][26] In other models of corneal injuries like alkali burns, the onset of NV is two to three days following injury and it affects all the eyes exposed. 46 The question why specific eyes are more vulnerable to the late response of HD than others is still open.…”

Section: The Delayed Phasementioning

confidence: 99%

Characterization of acute and delayed ocular lesions induced by sulfur mustard in rabbits

Kadar

Turetz²,

Fishbine³

et al. 2001

Current Eye Research

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“…Postexposure, steroidbased anti-inflammatory protocols reduce and postpone the appearance of late injury. However, they do not prevent late injury, suggesting that anti-inflammatories fail to treat the central pathology response for MGK onset (Amir et al, 2000;Kadar et al, 2009;Gordon et al, 2010). The distinct pathophysiology of MGK revealed in these studies suggests the involvement of pathophysiologies that operate on different time scales and in different corneal compartments than during the acute injury.…”

Section: Mechanistic Studies Of Hd Toxicitymentioning

confidence: 87%