Retinal morphology and ERG response in the DBA/2NNia mouse model of angle-closure glaucoma

PURPOSE. TO document the time course of retinal dysfunction by scotopic ele ctroretinography (ERG) and by quantitative morphology in eyes of the DBA/2N Nia substrain of mouse (DBA) with inherited angle-closure glaucoma. METHODS. DBA and control C57BL/6J (C57) mice were studied by ERG recordings from 5 to 15 months of age, and by morphology from 1 to 14 months of age. Scotopic ERGs were simultaneously recorded from both eyes of dark-adapted a nesthetized mice. Changes in the central neuronal retina were evaluated by quantitative morphometry performed on serial semithin sections of Epon-embe dded eyes. RESULTS. When compared with normal C57 mice, DBA mice showed significant re ductions of the a-wave and b-wave amplitudes by 7 to 8 months, and the decl ine continued as the animals aged. The b-wave implicit time in DBA mice sho wed a gradual prolongation beginning at 8 months of age, when compared with C57 mice. Logistic regression analyses revealed significant correlations i n a- and b-wave amplitude reductions between ipsilateral and contralateral eyes of DBA mice at ages when ERG parameters were greatly altered. Morpholo gically, thinning of the whole retina was already evident in DBA mice at 4 months of age, but loss of ganglion cells and thinning of the outer plexifo rm layer were first seen in 7- to 8-month-old animals. These changes progre ssed to the end of the 13-month period studied. CONCLUSIONS. Progressive thinning of the outer retinal layers in DBA mice w as found to correlate with decreases in ERG a- and b-wave amplitudes, both occurring from the age of 7 to 8 months onward. Similarities with the findi ngs in human late-stage glaucomatous retinopathy indicate the relevance of this animal model in further glaucoma research.