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Ruilin Wang, Caihui Jiang, Michael Young; Monitoring Morphological Changes in the Retina of Rhodopsin-/- Mice with SD-OCT. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4168.
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Retinitis pigmentosa (RP) and Age-related macular degeneration (AMD) are two major retinal degenerative diseases that cause irreversible blindness. Rodent models are very important tools for us to understand these diseases. Previous studies showed that rhodopsin is an essential element in photo-transduction and a structural protein in rod outer segment. Rhodopsin-/- mice do not express rodopsin and losing rod photoreceptors within a few months postnatal. We use Spectral Domain Optical Coherence Tomography (SD-OCT) to monitor the dynamic morphological changes in the retina of rhodopsin-/- mice.
Rhodopsin-/- C57Bl6 mice and wild type C57Bl6 mice at age 3, 6, 9 and 12 weeks were investigated using SD-OCT to obtain cross-sectional images of retina. Radial volume scan (centered on optic disc, diameter 1.3 mm) was used, each volume consisted 100 B-scans (1,000 A-scans per B-scan). And the outer nuclear layer (ONL) thickness was measured from selected scans. Histological examination (semi-thin cross-section of retina, H&E staining) was performed at each time point to compare with the OCT data. Dark adapted electroretinogram (ERG) was performed to correlate the morphological and functional changes in rhodopsin-/- mice.
SD-OCT showed that the ONL thickness in rhodopsin-/- mice was gradually decreased through week 3 to week 12 postnatal. The average thickness of ONL at 3, 6, 9 and 12 week were 40.6 ± 1.61μm, 27.9 ± 1.65μm, 14.5 ± 0.7μm and 6.0 ± 0.78μm, respectively. The outer segment layer was not detectable in rhodopsin-/- mice. The histological examinations identified the same trend. At 3 weeks, Rhodopsin-/- mice had 9 - 10 nuclei in the ONL while wild type mice had 11 - 12 nuclei. At 12 weeks, the number of nuclei dramatically decreased to 1-2 in rhodopsin-/- mice but no significant change in wild type mice. The ERG in rhodopsin-/- mice showed no distinct a wave, and b wave amplitudes decreased gradually in concordant with anatomical changes. The average b wave amplitudes at 3, 6 and 9 weeks were 196.8 ± 32.6μV, 179.7 ± 26.4μV and 118.3 ± 27.6μV. There was no apparent morphological and functional change in the wild type C57Bl6 mice at all time points (the average ONL thickness was 52.5 ± 0.69μm, and the average b wave amplitude was 673.9 ± 7.0μV).
The findings of the SD-OCT observation identified that the thickness of the ONL obviously decreased from week 3 to week 12 in rhodopsin-/- mice, but no observable changes in wild type mice. This phenomenon was also confirmed using the histological examinations on the the number of nuclei in the ONL and quantified amplitude of ERG. Therefore, SD-OCT can be a useful and non-invasive way to monitor the disease progress and the morphological changes in retina degenerative animal models.
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