Establishment of the ocular hypertension model using the common marmoset
Introduction
Glaucoma is a slowly progressive and irreversible ocular disease that is one of the leading causes of blindness worldwide. Increasing attention is being paid to evaluating the appearance of the optic nerve head and peripapillary retina in the diagnosis of glaucoma, especially in its early stage. Glaucoma pathology has been extensively studied at the level of the retinal ganglion cells (RGC) and optic nerve using rodents (mice, rats, and rabbits) (Aihara et al., 2003; Bunt-Milam et al., 1987; McKinnon et al., 2002) and non-human primates [mainly macaque monkeys such as rhesus (Macaca mulatta) and cynomolgus monkeys (Macaca fascicularis)] (Quigley and Hohman, 1983). Rodents such as mice, rats, and rabbits are most commonly used in basic research into glaucoma and drug screening (Hare et al., 2001), because they are small and easy to handle and low cost, and transgenic animals are readily available. However, the anatomy of the retina and optic nerve in rodents is different from those in humans, as are the structures and functional roles of visual pathways including the lateral geniculate nucleus and superior colliculus from the retina. Briefly, in rodents the major site of the retinal axon terminal is the superior colliculus, whereas in primates it is the lateral geniculate nucleus. Therefore, non-human primates such as rhesus and cynomolgus monkeys are widely used in experimental animal models of glaucoma (Quigley and Hohman, 1983). However, these animals are difficult to handle and breed. By contrast, the common marmoset (Callithrix jacchus) is a small New World monkey, the adult weighing 200–500 g, and they are easy to handle and breed (Ingram, 1975; Layne and Power, 2003). Recently, Sasaki et al. (2009) succeeded in producing transgenic common marmosets. Accordingly, the common marmoset is regarded as an attractive option for use as an animal model in a basic study.
In the present study, we established an experimental glaucoma model in the common marmoset, using argon-laser trabeculoplasty through a single-mirror goniolens.
Section snippets
Animals
The 4 adult female common marmosets used in this study, aged 2–3 years and weighing 250–350 g, were housed (Fig. 1A) in an air-conditioned room at 24–27 °C with 40–70% humidity. The marmosets were fed 30 g of New World monkey pellets (SPS, Oriental Yeast, Tokyo, Japan) supplemented with small portions of banana, apple, raisin, sweet potato, boiled egg, and yogurt. Additionally, 2 ml milk was given once a week, and a mealworm was given once or twice a month. Extra food deprivation was not
Gonioscopy of anterior chamber and direct laser photocoagulation to trabecular meshwork in common marmosets
The common marmoset is a small New World monkey (Fig. 1A). An ocular fundus image showed that the structures of the optic disc and vasculatures in the retinal surface were similar to those in humans and more commonly used macaque monkeys, and the fovea was clearly observed (Fig. 1B). In this study, we developed a single-mirror goniolens (Fig. 1C–F) for producing an experimental model of glaucoma in common marmosets. During gonioscopic examination, the iris, trabecular meshwork, and ciliary body
Discussion
In this study, chronic elevation of IOP in the common marmoset produced an enlarged cupping of the optic nerve head in ophthalmoscopy. These changes were similar to those seen in glaucoma patients and in ocular hypertension models (experimental glaucoma models) of a macaque monkey such as cynomolgus, rhesus, and Japanese monkeys (Macaca fuscata) (Ito et al., 2009; Quigley and Hohman, 1983; Sasaoka et al., 2008; Shimazawa et al., 2006). To date, non-human primates such as rhesus and cynomolgus
Acknowledgments
This study was supported in part by Grant-in-Aid for Scientific Research (C) (No. 23592612) and (B) (No. 22390321) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, by Takeda Science Foundation, and by the Cooperative Research Program of Primate Research Institute, Kyoto University (2010 and 2011).
References (25)
- et al.
Optic nerve head axonal transport in rabbits with hereditary glaucoma
Exp. Eye Res.
(1987) - et al.
Effect of general anesthetics on IOP in elevated IOP mouse model
Exp. Eye Res.
(2011) - et al.
Efficacy and safety of memantine, an NMDA-type open-channel blocker, for reduction of retinal injury associated with experimental glaucoma in rat and monkey
Surv. Ophthalmol.
(2001) - et al.
Morphological changes in the visual pathway induced by experimental glaucoma in Japanese monkeys
Exp. Eye Res.
(2009) - et al.
The patterns of retinal ganglion cell death in hypertensive eyes
Brain Res.
(1998) - et al.
Morphologic changes in the lamina cribrosa correlated with neural loss in open-angle glaucoma
Am. J. Ophthalmol.
(1983) - et al.
Changes in visual fields and lateral geniculate nucleus in monkey laser-induced high intraocular pressure model
Exp. Eye Res.
(2008) - et al.
Morphometric evaluation of changes with time in optic disc structure and thickness of retinal nerve fibre layer in chronic ocular hypertensive monkeys
Exp. Eye Res.
(2006) - et al.
Aspects of common marmoset basic biology and life history important for biomedical research
Comp. Med.
(2003) - et al.
Experimental mouse ocular hypertension: establishment of the model
Invest. Ophthalmol. Vis. Sci.
(2003)
Deformation of the lamina cribrosa and anterior scleral canal wall in early experimental glaucoma
Invest. Ophthalmol. Vis. Sci.
Slow intrinsic rhythm in the koniocellular visual pathway
Proc. Natl. Acad. Sci. U.S.A.
Cited by (11)
The eye and ocular adnexa of the non-human primate
2023, Spontaneous Pathology of the Laboratory Non-human PrimateWhole-globe biomechanics using high-field MRI
2017, Experimental Eye ResearchCitation Excerpt :First, we have only demonstrated the feasibility for conducting ex vivo biomechanics studies. Our scanner is designed for small animal imaging with a small bore, and would not be able to accommodate a live large animal such as a sheep, but could potentially be used to study small animals with lamina cribrosas, such as marmosets (Shimazawa et al., 2013). However, high-field, 9.4 T clinical MRI systems are becoming more common, meaning that the same measurements we have obtained in this study could potentially be obtained in a large animal in vivo.
Mechanistic Insights into Pathological Changes in the Diabetic Retina: Implications for Targeting Diabetic Retinopathy
2017, American Journal of PathologyCitation Excerpt :Significant impediments in using the primate model for DR research currently are the long durations for retinopathy to develop in primates, and the cost involved in maintaining these primates in institutional animal research facilities over that interval. The common marmoset, a new world primate, has been shown to be an excellent model for studying diseases, including ocular diseases such as exudative age-related macular degeneration with choroidal neovascularization, glaucoma, and myopia.113–116 Experimentally galactosemic marmosets recently have been shown to develop lesions that are characteristic of nonproliferative DR in patients (including degenerate capillaries, microaneurysms, and vascular permeability) within 2 years of disease onset.117,118
Ophthalmology of primatomorpha: Lemurs, tarsiers, monkeys, apes, and relatives
2022, Wild and Exotic Animal OphthalmologyA Robust Microbead Occlusion Model of Glaucoma for the Common Marmoset
2022, Translational Vision Science and TechnologyRecent advances in genetically modified animal models of glaucoma and their roles in drug repositioning
2019, British Journal of Ophthalmology