Keratoconus in a Cynomolgus Monkey

Kodama, Rinya; Yang, Xiuying; Araki, Tomoaki; Sato, Masato; Iwashige, Shuichiro; Tanigawa, Yohei; Uchimura, Mie; Ishimaru, Keisuke; Sasaki, Yuji; Kamimura, Yasuhiro; Maeda, Hiroshi

doi:10.1293/tox.23.53

Cited by 6 publications

(3 citation statements)

References 29 publications

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“…In a presentation on the examination and evaluation of the retina, Sorden (2015) reported cystic retinal degeneration at the ora serrata, glial nodules, optic atrophy, and outer retinal degeneration in cynomolgus monkeys. There are a few other descriptions of background lesions in case reports including optic atrophy (Dubielzig et al 2009), keratoconus (Kodama et al 2010), macular degeneration (Suzuki, Terao, and Yoshikawa 2003), and cataract (Sasaki et al 2011). In this publication, we report background changes that were observed after an extensive histopathologic examination of cynomolgus monkeys of Mauritian origin.…”

Section: Discussionmentioning

confidence: 99%

Spontaneous Findings in the Eyes of Cynomolgus Monkeys (Macaca fascicularis) of Mauritian Origin

Woicke

Hailé²,

Mysore

et al. 2018

Toxicol Pathol

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Spontaneous findings noted in the eyes of Mauritian cynomolgus monkeys are described and descriptions are supplemented with illustrations. Findings observed after extensive histopathologic examinations (20 to 44 sections per eye) from 20 control, 17 treatment-naive stock monkeys, and 2 findings noted in drug-treated monkeys that were considered to be spontaneous are included. Also included are findings from 361 control monkeys of routine toxicity studies performed at our laboratories, for most of which a standard histopathological examination of 1 section per eye was conducted. Common observations in monkeys examined extensively and in historical controls were limited to lymphocytic or mononuclear cell infiltrations of the uvea and/or conjunctiva/sclera and, less commonly observed, melanocytoma of the ciliary body or iris. Findings noted only in monkeys examined extensively consisted of inflammation of the conjunctiva, ora serrata cysts, glial nodules, focal degeneration of the retina, cystoid degeneration of the central retina, ballooning degeneration of the ciliary epithelium, cyst of the ciliary body, and decreased pigmentation of the retinal pigment epithelium. Changes recorded only in historical controls included retinal atrophy and nuclear displacement in the retina. Lesions are discussed and compared with pertinent literature.

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Section: Discussionmentioning

confidence: 99%

Spontaneous Findings in the Eyes of Cynomolgus Monkeys (Macaca fascicularis) of Mauritian Origin

Woicke

Hailé²,

Mysore

et al. 2018

Toxicol Pathol

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“…Therefore, nonhuman primates are a potentially valuable animal model for investigating macular diseases of humans. A variety of spontaneous ocular lesions were reported in cynomolgus monkeys used in toxicity studies 11 , 64 , 65 , 66 , 67 . Lesions of the fundus have been reported in a study providing a representative overview of more than 2000 monkeys having a 7.9% incidence of ocular lesions and 6.6% incidence of fundus lesions 11 .…”

Section: Spontaneous and Toxic Ocular Lesions In Laboratory Animalsmentioning

confidence: 99%

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

et al. 2015

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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.

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“…13 This shorter delay in the C max of rats compared with monkeys might be caused by differences in the sizes of ocular tissues between these species. For example, the thickness of the cornea is *130 and 600 mm in rats 21 and monkeys, 22 respectively. The more extensive distribution of radioactivity in the anterior and posterior ocular tissues than the plasma through 24 h after dosing suggests the direct delivery of tafluprost-derived materials to the inside of the eyes.…”

mentioning

confidence: 99%

Metabolism and Ocular Tissue Distribution of an Antiglaucoma Prostanoid, Tafluprost, After Ocular Instillation to Monkeys

Fukano

Kawazu

Akaishi

et al. 2011

Journal of Ocular Pharmacology and Therapeutics

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Topically administered [(3)H]tafluprost was well absorbed into the ocular and systemic tissues of the primary nonclinical species, monkey. The amount of the pharmacologically active form, that is, tafluprost acid, was high enough to occupy the target FP receptors at the site of action. The pharmacokinetic and metabolic properties of this difluorinated prostaglandin in primates are believed to result in clinical benefits of a long-term IOP-lowering effect.

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Keratoconus in a Cynomolgus Monkey

Cited by 6 publications

References 29 publications

Spontaneous Findings in the Eyes of Cynomolgus Monkeys (Macaca fascicularis) of Mauritian Origin

Spontaneous Findings in the Eyes of Cynomolgus Monkeys (Macaca fascicularis) of Mauritian Origin

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

Metabolism and Ocular Tissue Distribution of an Antiglaucoma Prostanoid, Tafluprost, After Ocular Instillation to Monkeys

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