P 338
Glaucoma animal models: Evaluation of widespread retinal dysfunction using electroretinography
A. U. Bayer, P. Cook, S. E. Brodie, T. Mittag
Purpose: Recent studies in patients with glaucoma found damage of photoreceptors in addition to neuropathy of the optic nerve. The purpose of the current study was to document progression of glaucomatous retinal pathology in mouse, rat, and monkey eyes with chronically elevated intraocular pressure (IOP) by flash electroretinography (ERG).
Methods: Animals followed were 16 normal C57/BL6 mice (controls) and 16 DBA/2NNia mice developing inherited angle-closure glaucoma associated with an increase of IOP (5 to 17 months of age), 12 rats with unilateral glaucoma induced by cautery of 3 extra-orbital veins (elevated IOP of 12 months duration), and 8 cynomologus monkeys with unilateral laser-induced glaucoma (12 months post-surgery). Scotopic and light-adapted ERG's were simultaneously recorded from both eyes of anesthetized animals.
Results: When comparing to normal C57/BL6 mouse eyes and contralateral normal rat or monkey eyes, a-wave and b-wave amplitudes as well as sum of oscillatory potentials were significantly reduced in DBA/2NNia mouse eyes as early as 7 months after birth and in rat and monkey eyes with elevated IOPs as early as 1 month post-surgery. In all mice, rats, and monkeys, ERG amplitude reductions were paralleled by prolongations of implicit times.
Conclusion: In rodent and monkey glaucoma models, amplitude reductions and peak-time prolongations of various components of scotopic (mainly rod-mediated) and light-adapted cone-mediated ERGs suggest widespread outer retinal dysfunction. These findings explain some of the abnormalities of color vision, swelling and loss of photoreceptors, and electrophysiological effects that have been observed in patients with glaucoma. Therefore, "glaucomatous retinopathy" needs to be further investigated.
Department of Ophthalmology, Mount Sinai Medical Center, 1 Gustave L. Levy Place, New York, New York, USA