Establishment of the ocular hypertension model using the common marmoset

https://doi.org/10.1016/j.exer.2013.03.010Get rights and content

Highlights

  • We developed a single-mirror goniolens for the common marmoset.

  • We succeeded in producing an experimental glaucoma model in the common marmoset.

  • The common marmoset is a small primate and easy to handle and breed.

  • The common marmoset could be also used as transgenic animals.

  • This model may be useful in elucidating the pathophysiological mechanisms.

Abstract

The purpose of this study was to establish an experimental glaucoma model in the common marmoset (Callithrix jacchus). Chronic intraocular pressure (IOP) elevation was induced by laser trabeculoplasty twice at 2-week intervals in the left eyes of 4 common marmosets. IOP was measured before and at 4, 7, 8, 11, 13 weeks after first laser treatment, and ophthalmoscopic examinations were also performed. At 13 weeks after laser treatment, each eye was enucleated, and retinal cross-sections and optic nerve were prepared for histological examination. Mean IOP values measured at the above 5 time points were over 40 mmHg in laser-treated eyes in 3 marmosets, but IOP in one marmoset was transiently increased to 26.6 mmHg at 7 weeks and then declined to the baseline level. In ophthalmoscopy, deepened and enlarged optic disc cupping, depending on the extent of IOP elevation and duration, were observed in laser-treated eyes of 3 marmosets with persistent IOP elevation, but there was no apparent change in the optic disc in the laser-treated eye of one marmoset with transient IOP elevation. Histological examination showed marked atrophy with deepened and enlarged cupping of optic disc, thinning of retinal nerve fiber layer and retinal ganglion loss in the retina, and axonal atrophy and loss in the optic nerve, depending on the extent of IOP elevation and duration. In conclusion, we succeeded in producing an experimental glaucoma model in the common marmoset, and this model may be useful in elucidating the pathophysiological mechanism for glaucoma.

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).

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