Changes in morphology and visual function over time in mouse models of retinal degeneration: an SD-OCT, histology, and electroretinography study
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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/m2). 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.
Keywordsrd10 rd12 Retinal degeneration Longitudinal study Spectral-domain optical coherence tomography
We thank Hitomi Suetsugu for technical assistance and the Center for Anatomical, Pathological, and Forensic Medical Research for preparation of the histological sections. This study was supported by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Grand-in-Aid for Young Scientists No. 24791850 and for the Innovative Techno-Hub for Integrated Medical Bio-Imaging of the Project for Developing Innovation Systems No. 24249082). This study was also supported by grants from the Ministry of Health, Labour and Welfare of Japan and Japan Society for the Promotion of Science.
Conflicts of interest
T. Hasegawa, none; H.O. Ikeda, Grant (the Astellas Foundation for Research on Metabolic Disorders, the Japan Foundation for Applied Enzymology, the Uehara Memorial Foundation, YOKOYAMA Foundation for Clinical Pharmacology, Mochida Memorial Foundation, Japan Intractable Diseases Research Foundation, Japan Research Foundation for Clinical Pharmacology); N. Nakano, none; Y. Muraoka, none; T. Tsuruyama, None; K. O. Furuta, none; H. Kohda, none; N. Yoshimura, grant (Nidek, Topcon, Canon, Novartis Japan, Bayer, Santen, Senju), honorary (Nidek, Canon, Novartis Japan, Bayer, Santen, Senju), and consultant fee (Nidek, Canon).