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U. Wolfrum, T. Goldmann, N. Overlack, C. Mueller, J. M. Vetter, K. Nagel-Wolfrum; Subcellular Localization of Usher Syndrome Proteins in the Human Retina. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2494.
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The human Usher syndrome (USH) is the most frequent cause of inherited combined deaf-blindness. It is assigned to three clinical types and 12 genetically heterogeneous subtypes. USH is characterized by profound inner ear defects and Retinitis pigmentosa. In contrast to USH patients, USH rodent models undergo, if at all, a very mild retinal degeneration. So far, there is no explanation for this difference in the retinal phenotype. One possible explanation is that primates and rodent photoreceptor cells differ in structure and in the subcellular distribution of individual USH proteins. Here, we tested the latter hypothesis by analyzing the subcellular localization of USH1/2 molecules in human retinas.
We assessed the expression of USH1/2 proteins by Western blots and by immunohistochemistry on cryosections through human retinas. Furthermore, subcellular localization was analyzed using a combination of high resolution immunofluorescence and immunoelectron microscopy.
All USH1/2 proteins are expressed in photoreceptor cells of human retinas. As shown in rodents, USH1/2 proteins are associated with the ciliary region or localize to the outer segment of human photoreceptors. However, staining intensities of USH proteins significantly differed between rods and cones. In addition, a subset of USH proteins were identified in calycal processes which are prominent features of human photoreceptors.
There are significant differences between rodents and humans in the expression of USH1/2 proteins in retinal photoreceptors which can explain the lack of retinal USH phenotype in mice. In human defects in USH molecules may lead to disorganization of the USH protein network in calycal processes and thereby to the destabilization of photoreceptor outer segments.
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