Retinal degeneration in rhesus monkeys, Macaca mulatta. Survey of three seminatural free-breeding colonies

El-Mofty, Aly A.M.; Eisner, Georg; Balazs, Endre A.; Denlinger, Janet L.; Gouras, Peter

doi:10.1016/0014-4835(80)90075-5

Cited by 29 publications

(28 citation statements)

References 27 publications

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“…To our knowledge, there are few reports demonstrating IRD in nonhuman primates. 18,19 In this study, we first discovered a cynomolgus monkey family with RP among the pedigreed population.…”

Section: Discussionmentioning

confidence: 99%

Discovery of a Cynomolgus Monkey Family With Retinitis Pigmentosa

Ikeda

Nishiguchi

Miya

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To accelerate the development of new therapies, an inherited retinal degeneration model in a nonhuman primate would be useful to confirm the efficacy in preclinical studies. In this study, we describe the discovery of retinitis pigmentosa in a cynomolgus monkey (Macaca fascicularis) pedigree.METHODS. First, screening with fundus photography was performed on 1443 monkeys at the Tsukuba Primate Research Center. Ophthalmic examinations, such as indirect ophthalmoscopy, ERGs using RETeval, and optic coherent tomography (OCT) measurement, were then performed to confirm diagnosis. RESULTS.Retinal degeneration with cystoid macular edema was observed in both eyes of one 14-year-old female monkey. In her examinations, the full-field ERGs were nonrecordable and the outer layer of the retina in the parafoveal area was not visible on OCT imaging. Moreover, less frequent pigmentary retinal anomalies also were observed in her 3-year-old nephew. His full-field ERGs were almost nonrecordable and the outer layer was not visible in the peripheral retina. His father was her cousin (the son of her mother's older brother) and his mother was her younger half-sibling sister with a different father.CONCLUSIONS. The hereditary nature is highly probable (autosomal recessive inheritance suspected). However, whole-exome analysis performed identified no pathogenic mutations in these monkeys.

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“…To our knowledge, there are few reports demonstrating IRD in nonhuman primates. 18,19 In this study, we first discovered a cynomolgus monkey family with RP among the pedigreed population.…”

Section: Discussionmentioning

confidence: 99%

Discovery of a Cynomolgus Monkey Family With Retinitis Pigmentosa

Ikeda

Nishiguchi

Miya

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…Encouraged by the earlier findings of ElMofty et al [6,7] in a small sample at the CPRC, we concentrated our efforts on the aged segment of this closed primate popula tion. We confirmed the high incidence of clin ically detectable macular pathology in aged rhesus monkeys at an incidence much higher than previously observed in large surveys.…”

Section: Discussionmentioning

confidence: 99%

“…A much greater incidence of maculopathy in primates was reported by El-Mofty et al [6,7] who studied 162 seminatural free-ranging rhesus monkeys of all ages in the closed colo ny at the Caribbean Primate Research Center (CPRC) of the University of Puerto Rico. In their small sample of older adults ranging from 16 to 21 years of age, 83% of the animals showed pigmentary alterations or drusen-like changes.…”

Section: Introductionmentioning

confidence: 97%

Degenerative Changes in Maculas of Rhesus Monkeys

Engel¹,

Dawson

Ulshafer³

et al. 1988

Ophthalmologica

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In the hope of identifying an animal model for age-related macular degeneration (AMD) we undertook a pilot investigation of aged rhesus monkeys. Twenty-nine monkeys from a seminatural colony were examined at the Caribbean Primate Research Center. Macular drusen were found in 74% of the monkey eyes. Alterations of the retinal pigment epithelium within the macula were noted in 45% of the eyes. Fluorescein angiography in selected animals revealed window defects consistent with drusen. None of this sample showed the exudative form of AMD or disciform scarring. One typical monkey underwent special studies including measurement of visual resolution by electrophysiological study of the retinal and visual cortex. Application of human criteria to this animal supported the diagnosis of early AMD. Histopathologic study of one eye by transmission electron microscopy confirmed the presence of drusen with nearly identical ultrastructural features to those found in the human pigment epithelium in AMD.

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“…Funduscopic examination of these animals revealed macular drusen in approximately half of animals older than 9 years and all animals older than 25 years. 20,21,[29][30][31] Histology and ultrastructural studies confirmed the presence of small and large drusen within the Bruch's membrane and beneath the RPE. 19 A small breeding colony derived from these animals was established at the University of Florida in 1994 and so exhibits similar findings.…”

Section: Adult-onset Macular Degeneration In Rhesus Monkeys (Macaca Mmentioning

confidence: 84%

REVIEW PAPER: Animals as Models of Age-Related Macular Degeneration

Zeiss

2010

Vet Pathol

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Age-related macular degeneration (AMD) is a degenerative condition that begins in Bruch's membrane and progresses to involve the retinal pigment epithelium and ultimately the overlying photoreceptors. The only required etiologic factor is age, and AMD is regarded as the leading cause of blindness in individuals older than 65 years. AMD results from variable contributions of age, environment, and genetic predisposition. Many loci are linked to AMD; in the majority of cases, the disease is associated with polymorphisms within these genes, rather than mutations that ablate gene function. The etiologic complexity of AMD is reflected by the paucity of animal models that entirely replicate the human disease. This review compares the salient anatomy of the primate and rodent retina, particularly in the light of AMD pathology. It next discusses prevailing hypotheses explaining how AMD may develop. These include the role of complement activation and macrophage chemotaxis in AMD, molecular mechanisms of choroidal neovascularization, and the roles of oxidative damage and lipid metabolism. Finally, the article gives an overview of spontaneous and induced nonhuman primate models and describes relevant mouse models in the context of each pathogenetic mechanism. KeywordsBruch's membrane, choriocapillaris, complement, degeneration, macula, retinal pigment epithelium Age-related macular degeneration (AMD) is a progressive condition of the retinal pigment epithelium (RPE), its supporting basement membrane, and the overlying photoreceptor layer. It affects the macula, the central area of the retina responsible for high-acuity daylight vision. Among individuals older than 65 years, AMD is regarded as the leading cause of blindness in the industrialized world. 39AMD has no single cause and results from variable contributions of age, genetic predisposition, and environment. Established epidemiologic risk factors include cigarette smoking, diet, female sex, Caucasian race, and a family history of AMD.52,60,61 Because AMD is rare in individuals younger than 55 years, the only required risk factor is age, which implicates the multitude of cellular changes that accompany normal aging in the pathogenesis of AMD. The challenge is to identify how these are altered to tip the process toward overt disease.With age, most people accumulate small, well-demarcated deposits of extracellular material beneath the RPE. 5,45 These are known as small, hard drusen and are not pathogenic. However, if these deposits enlarge, they become associated with regional RPE loss and eventual degeneration of overlying photoreceptors. These changes are funduscopically visible, and their progression is used to classify lesions along the continuum of early to late dry AMD. 18 The pathogenetic mechanisms of this process center on inflammation, oxidative damage, and RPE senescence 45 and are predominantly modeled in the mouse.In the minority of cases, late AMD is accompanied by growth of blood vessels from the choroid through Bruch's membrane toward the retina. ...

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Retinal degeneration in rhesus monkeys, Macaca mulatta. Survey of three seminatural free-breeding colonies

Cited by 29 publications

References 27 publications

Discovery of a Cynomolgus Monkey Family With Retinitis Pigmentosa

Discovery of a Cynomolgus Monkey Family With Retinitis Pigmentosa

Degenerative Changes in Maculas of Rhesus Monkeys

REVIEW PAPER: Animals as Models of Age-Related Macular Degeneration

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