PATHOLOGY OF 6-AMINONICOTINAMIDE TOXICOSIS IN THE RABBIT (OCULAR, ULTRASTRUCTURE, EYE)

JAMES ARTHUR RENDER, Purdue University

Abstract

This research was conducted to characterize the toxicosis of 6-aminonicotinamide in the rabbit with special emphasis on ocular alterations. Competitive inhibition of nicotinamide in male and female New Zealand White and Dutch Belted rabbits by intraperitoneal injections of 6-aminonicotinamide produced hindlimb ataxia with progression to paresis and sometimes paralysis, diarrhea, anorexia and death. Principal gross lesions were cecal distention, cholecystic necrosis and iridal congestion. Light microscopic lesions were atrophy and necrosis of the Harder's gland and cytoplasmic vacuolation and atrophy of the seminiferous tubules with multinucleated giant cell formation. Epithelial cytoplasmic vacuolation was present in the following: epididymis, bile ducts, trachea, bronchi, pancreatic duct, adrenal cortex, urinary bladder, subcommissural organ, cecum, sacculus rotundus, vermiform appendix and gall bladder. Epithelial intracytoplasmic vacuoles were present the inner epithelial layer of the iris and ciliary body and the outer epithelial cell layer of the ciliary body, especially in the iridal and anterior ciliary processes. Ciliary vacuoles consisted of communicating cavities in ultraplaned sections viewed by scanning electron microscopy. Cytoplasmic vacuolation caused cellular swelling which, along with stromal edema and fibrin exudation, caused thickening of the ciliary processes when viewed by scanning electron microscopy. Cytoplasmic vacuolation and contraction of the iris caused distortion of iridal radial folds when the posterior surface of the iris was viewed by scanning electron microscopy. The retinal outer plexiform layer was vacuolated due to intracytoplasmic vacuoles in photoreceptor cell axons and the retinal pigment epithelium was vacuolated due to marked distention of intercellular spaces. Epithelial intercellullar spaces were mildly dilated in the iris, ciliary body and gall bladder and cholecystic epithelium contained intracytoplasmic vacuoles similar to those within the uveal epithelium. Ocular and certain systemic lesions were prevented by simultaneous administration of nicotinamide and no lesions were attributed to adminstration of nicotinamide.

Degree

Ph.D.

Subject Area

Pathology

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