Experimental glaucoma in the primate induced by latex microspheres
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.
Section snippets
Materials and methods
Four rhesus monkeys (Macaca mulatta), of both sexes, were used in this study (Table 1). All had clinically normal appearing eyes, as determined by slitlamp biomicroscopy, gonioscopy, and stereoscopic funduscopy, and all had baseline intraocular pressures, measured under ketamine HCl anesthesia with a Tono-pen XL tonometer (Mentor O&O, Norwell, MA), below 21 mmHg (normal IOP for ketamine-anesthetized rhesus monkeys ∼15 mmHg). Topical proparacaine HCl (Alcaine®, 0.5%, Alcon Laboratories, Ft
Results
Microspheres infiltrated with fluorescein dye were used in order to monitor their movement and deposition within the eye non-invasively using the slitlamp, goniolens, and a cobalt filter. Beads of 10 μm diameter size were chosen based on their ease of viewing with the cobalt filter of the slit lamp (because they were designed for blood flow determination, they are more heavily labeled than other fluorescent microspheres), and the fact that they are significantly larger than most of the
Discussion
In primates, intraocular pressure is maintained at about 15 mmHg by a balance in the production and outflow of aqueous humor within the anterior segment of the eye. Aqueous humor, which provides nutrients and removes metabolites for the avascular lens and cornea, is released from the ciliary processes in the posterior chamber and returned to the venous system by passing through multiple connective tissue plates that form the trabecular meshwork (TM) in the anterior chamber angle (Samuelson, 1996
Acknowledgements
The authors wish to thank Dan Kunkle from Kunkle Medical Technologies for use of the Nikon FS-3 Zoom Photo Slit Lamp, and Ken Christopherson from Retina Photographic for assistance with the photo slit lamp and fundus photography. They also thank Dr Rosario Hernandez and Belinda McMahan from Washington University-St. Louis, for preparing the optic nerve materials, and Ms Judy McMillan for assistance with the animals and axon measurements. This work was supported in part by The Glaucoma
References (24)
- et al.
Aqueous humor pathways through the trabecular meshwork and into Schlemm's canal in the cynomolgus monkey (Macaca irus). An electron microscopic study
Am. J. Ophthalmol.
(1972) - et al.
A rat model of chronic pressure-induced optic nerve damage
Exp. Eye Res.
(1997) An experimental method to produce angle block in rabbits and the use of phospholine iodine after angle block avoiding paracentesis reflex
Am. J. Ophthalmol.
(1962)- et al.
Chronic ocular hypertension following episcleral venous occlusion in rats
Exp. Eye Res.
(1995) - et al.
Experimental glaucoma model in the rat induced by laser trabecular photocoagulation after an intracameral injection of India ink
Jpn. J. Ophthalmol.
(1998) Animal models of glaucoma
Histopathology of retina and optic nerve with experimental glaucoma
Arch. Ophthalmol.
(1962)- et al.
Morphology of the trabecular meshwork and inner-wall endothelium after cationized ferritin perfusion in the monkey eye
Invest. Ophthalmol. Vis. Sci.
(1991) - et al.
Experimental glaucoma in the rhesus monkey
Invest. Ophthalmol.
(1974) - et al.
Abolition of the electroretinogram following injection of α-chymotrypsin into the vitreous and anterior chamber of monkey
Arch. Ophthalmol.
(1965)
Obstruction of the outflow of aqueous humor produced experimentally
Acta Ophthalmol.
Experimental glaucoma in monkeys. I. Relationship between intraocular pressure and cupping of the optic disc and cavernous atrophy of the optic nerve
Arch. Ophthalmol.
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