The metabolic and molecular basis of spontaneous ophthalmic conditions in animals hold the key to the development of new and more effective therapeutic modalities. Hence, additional investigations are indicated, especially in the dog, to permit greater understanding into the basic mechanisms of both the normal and diseased eye.

To investigate the relationships between the tapetal discoloration and chemical structure activity, beagle dogs were given a single intravenous administration of metabolites or analogs of a synthesized chymotrypsin inhibitor, FK-401.

The alcoholic metabolite of FK-401 caused discoloration in the tapetum lucidum. Numerous alcoholic analogs with a tertiary amine side chain also caused tapetal discoloring. However, no histopathological changes were observed in the tapetum layer. Ethambutol had a similar action.

These results suggested that some alcoholic compounds with a tertiary amine could induce discoloration of the tapetum lucidum in the canine eye.

A single subcutaneous injection of 3 mg/kg cisplatin (CDDP) to 1- and 6-day-old rats caused retinal lesions, but no lesions were observed in 13-day-old rats. The lesions consisted of decreased mitosis, karyopyknosis and karyorrhexis of the retinal neuroblastic cells which appeared within 6 hours after the injection. The lesions progressed with time with a peak response at 48 hours. Electroretinograms 40 days after a single subcutaneous injection of 1.8 mg/kg CDDP to 1-day-old rats showed decreased a- and b-wave amplitudes and elongation of the implicit time of the b-wave. These rats with ERG abnormality showed retinal atrophy including narrowing of the retinal outer nuclear layer, especially in the peripheral portion of the retina.

Drug-induced retinal degeneration was found in rats used for a subacute toxicity study. Light microscopically, there were folds or rosette formation in the outer and inner granular layer, edema of the layer of rods and cones, deposition of basophilic materials in the cavum subretina, swelling, degeneration and proliferation of the pigment cells, transmigration of the pigment cells and macrophages into the retina, and inflammatory cell infiltration in the chorioidea. Electron microscopically, there was accumulation of needle crystalloid substance in the swollen pigment cells, and electrondense materials in the pigment cell layer which were assumed to be debris of the outer segment.

The changes were found in rats kept for 28 days without the drug, an amphyphilic cationic compound, after completion of 28 days of treatment. But animals killed at the end of drug treatment for 28 days showed only slight swelling of the pigment cells.

We evaluated a short-term test method for retinal toxicity induced by chloroqine in rabbits. We injected 2 and 4 mg/eye chloroquine intravitreally into one eye of albino and pigmented rabbits (test eye), and saline into other (control eye). After the treatment, we examined the retinal toxicity of the test substance by electroretinogram (ERG; the a-, b- and c-waves and the oscillatory potentials). The ERG of both eyes was recorded periodically at the same time for four weeks and compared between test and control eyes.

Intravitreal injection of chloroquine caused clear by diminished amplitude and prolongated latency of the b-wave and oscillatory potentials, in both types of rabbit and at both dosages. The results indicated that chloroquine has retinal toxicity. With our method, the retinal toxicity of chloroquine in rabbits can be evaluated quickly by intravitreal injection and electrophysiological recording (ERG). We think that our method is useful for evaluating the retinal toxicity of chemical substances which have affinity for melanine and pass easily into the eyeball.

An iris tumor was found in a 107-week-old male Fischer 344/DuCrj rat. At necropsy, the iris of the right eye showed grayish-white discoloration and thickening. Histologically, the tumor was confined to the iris. The tumor was mainly composed of spindle-shaped cells arranging densely and in bundle and whorl patterns. The neoplastic cells had the slightly eosinophilic cytoplasm and elongated, oval nuclei. No mitotic figure was seen. Collagenic fibers, elastic fibers, myofibers, and reticulin fibers were not increased in the tumor. Immunohistochemically, the spindle-shaped cells reacted positively to anti-S100 protein antibody. The present case was diagnosed as a benign iris tumor arising from amelanotic pigmented cells in the iris stroma.

We examined forty-seven cynomolgus monkeys with normal ophthalmoscopic findings, seventeen monkeys with bilateral ocular abnormalities, and eight monkeys with unilateral ocular abnormalities for their visual function, using the simplified method for judging visual function of the cynomolgus monkey, which was established previously (Suzuki et al., 1988). The monkeys with bilateral ocular abnormalities were inferior in their visual function to the monkeys with normal fundus. The monkeys with unilateral ocular abnormalities showed about the same degree in their visual function as the monkeys with normal fundus.