Experimental glaucoma in the primate induced by latex microspheres

Abstract

The injection of sterile latex microspheres into the anterior chamber of the eye is presented as a simple and cost effective method for inducing chronic elevation of intraocular pressure (IOP) and experimental glaucoma in primates. The microspheres produce elevated IOP primarily by restricting the outflow of aqueous humor through the trabecular meshwork located in the chamber angle. Different levels and durations of elevated IOP can be obtained by altering the frequency and number of microspheres injected. In comparison with other primate models of experimental glaucoma, the approach described here has the advantages of producing chronic elevations of IOP without the need for expensive ophthalmic equipment and personnel, surgical intervention or intraocular inflammation, and without compromising visibility of the optic disc, which is necessary for clinical assessment of the onset and progression of the disease.

Introduction

Much of our current understanding of the damaged or diseased nervous system is derived from animal models. Such models offer a number of advantages over the use of human tissues. Foremost among these is the ability to examine both the onset and progression of pathogeny in a controlled and reproducible manner. In addition, most animal models also permit one to study the disease process over a much shorter time period than that which occurs naturally. Ideally, an animal model should: (1) be technically easy to carry out; (2) provide consistent results that are applicable to the human disease process; (3) induce minimal secondary effects; and (4) be cost effective.

Over the past several years, we have been interested in the degenerative effects that chronic elevation of intraocular pressure (IOP), a risk factor commonly associated with glaucoma, has on the neuronal organization of the primate visual system (Weber et al., 1998, Weber et al., 2000). However, like other chronic diseases, glaucomatous optic neuropathy is difficult to study in humans because of the insidious nature of the disease, and the fact that it is most common in older individuals (Wilensky, 1994), where the identification of pressure-specific degenerative changes often is confounded by other medical conditions. For these reasons, much effort over the years has focused on the development of an animal model of pressure-induced experimental glaucoma (see Chew, 1996 for review). The various approaches used have ranged from obstruction of the extraocular veins (Huggert, 1957, Shareef et al., 1995, Morrison et al., 1997), to intraocular insertion and injection of a variety of materials (Huggert, 1957, DeCarvalho, 1962, Kupfer, 1962, Samis, 1962, Hamasaki and Ellerman, 1965, Kalvin et al., 1966, Lessell and Kuwabara, 1969, Quigley and Addicks, 1980, Levy, 1974), to laser scarification of the trabecular meshwork (Gaasterland and Kupfer, 1974, Quigley and Hohman, 1983, Ueda et al., 1998). While each method has proved effective in elevating IOP, none has met all of the previously-stated criteria. Complications such as iridocyclitis, obscured visibility of the optic disc, keratitis and corneal neovascularization, and fixed mydriasis have been reported. In addition, many of these procedures require surgical intervention and/or access to expensive and highly specialized ophthalmic equipment and personnel.

In the present study, we describe a method whereby chronic elevation of intraocular pressure and glaucoma is induced in the primate eye by periodic injection of sterile latex microspheres into the anterior chamber of the eye. The procedure is simple and reproducible, produces little or no inflammatory response, permits continued clinical evaluation of the posterior region of the eye, and provides a good level of control over the range and duration of elevated IOP. In addition, the microspheres are commercially available, can be obtained in a variety of sizes and fluorescent coatings, and are relatively inexpensive.