Changes in morphology and visual function over time in mouse models of retinal degeneration: an SD-OCT, histology, and electroretinography study

Tomoko Hasegawa, Hanako O. Ikeda, Noriko Nakano, Yuki Muraoka, Tatsuaki Tsuruyama, Keiko Okamoto-Furuta, Haruyasu Kohda, Nagahisa Yoshimura

To examine the long-term natural course of retinal degeneration in rd10 and rd12 mice using serial spectral-domain optical coherence tomography (SD-OCT), electroretinography/electroretinograms (ERGs), and histological analysis. Photoreceptor layer thickness and the ability to visualize photoreceptor ellipsoid zones were analyzed using SD-OCT images, and these images were compared with hematoxylin and eosin-stained sections and electron microscopy images. The a- and b-wave amplitudes of the ERGs were analyzed. In rd10 mice, the photoreceptor layer thickness rapidly decreased, and the photoreceptor ellipsoid zone was visible on SD-OCT images in 89 and 43 % of eyes of 21 and 33-day-old mice, respectively. In rd12 mice, the photoreceptor layer gradually thinned, and the ellipsoid zone remained visible in 92 % of eyes at 19 months. Electron microscopy revealed that photoreceptor degeneration had occurred on the inner side of the outer nuclear layer in 21-day-old rd10 and 7-month-old rd12 mice, possibly due to autophagy mechanisms. Scotopic ERGs of rd10 mice showed a diminished response at 21 days; at 33 days, no response was detectable. In rd12 mice, scotopic ERGs were undetectable at 28 days (stimulus intensity 3.0 cds/m(2)). Photopic ERGs were nearly undetectable in 28-day-old rd10 mice, but a small b-wave was still recordable in 13-month-old rd12 mice. Our results demonstrate that visual function deteriorated with photoreceptor degeneration within 1 month in rd10 mice. In rd12 mice, however, the process of visual function deterioration and photoreceptor degeneration was still in progress at 13 months of age.