Ocular toxicity of gliotoxin and other selected mycotoxins
Abstract
The histopathologic alterations produced by intraocular administration of various mycotoxins were studied. The effects of intraocular administration of gliotoxin and patulin were evaluated in dose variation studies. The ocular inflammatory response and retinal degeneration induced by intraocular administration of gliotoxin were characterized clinically, ultrastructurally and by the effect on retinal nonprotein sulfhydryl concentrations. The acute toxity of orally-administered gliotoxin in the hamster was investigated. Intra-aqueously injected patulin at doses of 25-100 $\mu$g produced alterations of ulcerative keratitis and exudation into the anterior chamber of an essentially acellular proteinaceous fluid. Alterations were consistent with those of an ocular irritative response. Forty-eight hours following intravitreal administration of patulin at doses of up to 100 $\mu$g, ocular alterations were serous retinal detachment and degeneration, vitreal liquefaction and serous anterior chamber exudate. The mechanism of serous retinal detachment most likely involved alterations in permeability of chorioretinal vasculature. Intra-aqueous administration of gliotoxin produced alterations of ulcerative keratitis, anterior uveitis and proteinaceous and heterophilic exudate within the anterior chamber. Alterations were not dose dependent over the dose range studied. The intravitreal administration of gliotoxin produced suppurative endophthalmitis. Alterations of retinal degeneration and necrosis were most prominent in the rod and cone layer and were present at 12 hours, prior to the onset of suppurative inflammation. Ultrastructurally, retinal alterations were present 4 hours after intravitreal injection of 100 $\mu$g of gliotoxin. These were characterized by fragmentation of outer segment membrane discs and mitochondrial swelling in pigment epithelium and rod inner segments. Later, degeneration involved all retinal layers with retinal detachment. Alterations of ocular inflammation and retinal photoreceptor cell degeneration were consistent with oxidant injury to the retina. Gliotoxin, like sporidesmin, may generate superoxide and other reactive oxygen species.
Degree
Ph.D.
Advisors
Carlton, Purdue University.
Subject Area
Veterinary services
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