Characteristics of structures and lesions of the eye in laboratory animals used in toxicity studies

Abstract

Histopathology of the eye is an essential part of ocular toxicity evaluation. There are structural variations of the eye among several laboratory animals commonly used in toxicity studies, and many cases of ocular lesions in these animals are related to anatomical and physiological characteristics of the eye. Since albino rats have no melanin in the eye, findings of the fundus can be observed clearly by ophthalmoscopy. Retinal atrophy is observed as a hyper-reflective lesion in the fundus and is usually observed as degeneration of the retina in histopathology. Albino rats are sensitive to light, and light-induced retinal degeneration is commonly observed because there is no melanin in the eye. Therefore, it is important to differentiate the causes of retinal degeneration because the lesion occurs spontaneously and is induced by several drugs or by lighting. In dogs, the tapetum lucidum, a multilayered reflective tissue of the choroid, is one of unique structures of the eye. Since tapetal cells contain reflecting crystals in which a high level of zinc has been demonstrated chemically, drug-induced tapetum degeneration is possibly related to zinc chelation. The eye of the monkey has a macula similar to that of humans. The macula consists only of cones with a high density, and light falls directly on the macula that plays an important role in visual acuity. Macular degeneration occurring in monkeys resembles histopathologically that of humans. Hence, the eye of the monkey is a suitable model to investigate macular degeneration and to assess drug-induced macular lesions.

Keywords: eye; laboratory animals; lesions; structures.

Fig. 1.

Fundus and histology of the retina in rats. a) Normal features of the fundus in a 19-week-old male IGS rat. b) Severe retinal atrophy of a 58-week-old male Wistar rat. Note increased fundus reflection, atrophy of retinal vasculatures and pallor discoloration and edematous swelling of the optic disc. c) Normal features of the fundus in a 19-week-old male Zucker rat. Note the dark grayish discoloration of the fundus. d) Normal retinal structures of the same rat as in a). Note that there is no pigment deposition anywhere. e) Severe retinal degeneration of the same rat as in b). Note the loss of the outer retinal layers (photoreceptor layer, outer limiting membrane, outer nuclear layer and outer plexiform layer), disorganization and decreased cell numbers of the inner nuclear layer, decreased thickness of the inner plexiform layer and decreased number and shrinking of the ganglion cells. f) Normal retinal structures of the same rat as in c). Note the pigmentation in the retinal pigment epithelium, the choroid and interstitium of the sclera. HE stain. Bar = 100 µm.

Fig. 2.

Fundus, histology of the retina and gross appearance of the lens in beagle dogs. a) Normal features of the fundus in an 8-month-old male dog. Note the bluish-green coloration of the tapetum lucidum in an upper part of the retina. b) Normal retinal structures of the tapetum lucidum of the fundus of the same dog as in a). Note the multilayered tapetum cells between the retinal pigment epithelium (RPE) and the choroid and the decreased pigmentation of the RPE. c) Normal retinal structures of the non-tapetum portion of the retina of the same dog as in a). Note that there are no tapetum cells between the RPE and choroid. HE stain. Bar = 100 µm. d) Drug-induced decoloration of the tapetum lucidum in the retina of a 10-month-old male dog. The tapetum lucidum is changed to a light yellowish color. e) A Y-suture (arrowhead) of the lens in a 22-month-old male dog. The suture is normally observed in a posterior portion of the lens.

Fig. 3.

Fundus and histology of the retina in cynomolgus monkeys. a) Normal features of the fundus in a 6-year-old male monkey. Note the macula (arrowhead) beside the optic disc. b) Normal retinal structures of the macula in the retina of a 4-year-old female monkey. Note the pit formation (fovea) in the retina consisting of cones and a decreased number of other retinal cells. HE stain. Bar = 200 µm.