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PURPOSE: To document the time course of retinal dysfunction by scotopic electroretinography (ERG) and by quantitative morphology in eyes of the DBA/2NNia substrain of mouse (DBA) with inherited angle-closure glaucoma. METHODS: DBA and control C57BL/6J (C57) mice were studied by ERG recordings from five to 15 months of age, and by morphology from one to 14 months of age. Scotopic ERGs were simultaneously recorded from both eyes of dark-adapted anesthetized mice. Changes in the central neuronal retina were evaluated by quantitative morphometry performed on serial semithin sections of Epon-embedded eyes. RESULTS: When compared with normal C56 mice, DBA mice showed significant reductions of the a- and b-wave amplitudes by seven to eight months, and the decline continued as the animals aged. The b-wave implicit time in DBA mice showed a gradual prolongation beginning at eight months of age, when compared with C57 mice. Logistic regression analyses revealed significant correlations in a- and b-wave amplitude reductions between ipsilateral and contralateral eyes of DBA mice at ages when ERG parameters were greatly altered. Morphologically, thinning of the whole retina was already evident in DBA mice at four months of age, but loss of ganglion cells and thinning of the outer plexiform layer were first seen in seven- to eight-month-old animals. These changes progressed to the end of the 13-month period studied. CONCLUSIONS: Progressive thinning of the outer retinal layers in DBA mice was found to correlate with decreases in ERG a- and b-wave amplitudes, both occurring from the age of seven to eight months onward. Similarities with the findings in human late-stage glaucomatous retinopathy indicate the relevance of this animal model in further glaucoma research.
Dr T. Mittag, Department of Ophthalmology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029-6571, USA. thomas.mittag@mssm.edu
2.14 Optic disc (Part of: 2 Anatomical structures in glaucoma)
3.1 Microscopy (Part of: 3 Laboratory methods)
6.7 Electro-ophthalmodiagnosis (Part of: 6 Clinical examination methods)
5 Experimental glaucoma; animal models