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R. K. Crouch, B. Rohrer, W. Baehr, K. Palczewski, J. Fan; Disruption of the Retinoid Cycle in LRAT-/- and RPE65-/- Mice Results in Similar Patterns of Retinal Degeneration: Cone Opsin Mislocalization With Rapid Cone Degeneration and Slow Rod Degeneration. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5636.
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© ARVO (1962-2015); The Authors (2016-present)
To compare rod and cone degeneration in two mouse models where the retinoid cycle is disrupted.
The retina and RPE of age matched LRAT-/-, RPE65-/- and wild type mice were examined for pigment content by absorption measurements, rhodopsin phosphorylation by mass spectral analysis and photoreceptor cell ratios and morphology by immunohistochemistry using opsin specific antibodies and PNA lectin.
11-cis Retinal is not generated in these two models of retinoid cycle disruption, as reported previously. In both models, the 9-cis retinal rod pigment accumulates with dark rearing, although to a lesser extent in the LRAT-/- mice as compared with RPE65-/- mice. The rod opsin levels at 6 months were found to be the same in the two models, ~50% of wild type levels, indicating slow rod degeneration. The rod opsin in both models is phosphorylated (<15%) irrespective of light exposure. The number of PNA-lectin stained cones was found to be dramatically decreased at 3 weeks. The cone opsin mislocalization reported in the RPE65-/- mice with the opsin being distributed throughout the entire cone cell was also observed in the LRAT-/- animals.
In the absence of a normal retinoid cycle due to the disruption of the normal generation of 11-cis retinal, trace amounts of 9-cis retinal form and are incorporated into functional rod pigments. Relatively slow rod degeneration and early cone degeneration occurs in both models. Low levels of RPE65 have been shown to be present in mouse cones. However, as rapid cone degeneration and cone opsin mislocalization occur in the LRAT-/- model as well as in the RPE65-/- mouse, 11-cis retinal is apparently essential to normal cone opsin trafficking and to maintainence of functional cone photoreceptors.
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