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K. Nagel-Wolfrum, T. Goldmann, E. Sehn, G. Stern-Schneider, N. Overlack, U. Wolfrum; Subcellular Localization of Proteins Related to the Usher Syndrome in Human and Primate Retinas. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2718.
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The human Usher syndrome (USH) is the most frequent cause of inherited combined deaf-blindness in man. It is assigned to three clinical types and 12 genetically heterogeneous subtypes. In general, USH patients suffer from prepubertal or a later onset of retinal dystrophy. Molecular analyses of the diverse identified USH proteins revealed USH protein networks in synapses and ciliary compartments of rodent photoreceptors. Nevertheless, existing USH rodent models undergo, if at all, a very mild retinal degeneration. So far, there is no explanation for these differences between human USH patients and USH mouse models in the severity of retinal degeneration. Since this discrepancy may be due to differences between primates and mice in the photoreceptor cell structure and/or in the subcellular distribution of individual USH proteins we analyzed the localization of USH1and 2 molecules on subcellular level in primate retinas.
We assessed the expression of USH1and 2 proteins by immunocytochemistry of cryosections through human and macaque retinas. Furthermore, subcellular localization was analyzed using a combination of high resolution immunofluorescence and immunoEM.
All USH1 and 2 proteins are expressed in rod and cone photoreceptor cells of human and macaque retinas. As shown in rodents, USH1 and 2 proteins are localized in synapses and ciliary regions of human and macaque photoreceptors. However, staining intensities of USH proteins significantly differed between rods and cones. Furthermore, a subset of USH proteins were identified in calycal processes which are prominent features of primate photoreceptors.
There are significant differences between rodents and primates in the expression of USH1and 2 proteins in retinal photoreceptors which can explain the lack of retinal degeneration in mice. In human and primates, defects in USH molecules may lead to destabilization of calycal processes and thereby of photoreceptor outer segments. Furthermore, it is reasonable that the defects of the abundant USH1and 2 molecules in cones may affect cone-dominated primate retinas more than rod-dominated rodent retinas.
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