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T. Rezaie, M. Sarfarazi; Co-Localization of Optineurin With Its Interacting Proteins of Huntingtin, mGluR1a, FOS, RAB8, and Myosin-VI in Ocular Tissues of Rhesus Monkey. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3691.
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Mutations in the Optineurin (OPTN) gene are associated with the GLC1E-linked adult-onset primary open-angle glaucoma (Science 295:1077-1079; 2002). This study aimed to examine ocular expression of five optineurin-interacting proteins of Huntingtin (HTT), metabotropic Glutamate Receptor 1a (mGluR1a), FOS, RAB8 and Myosin VI (MYO6) in optic nerve and ocular tissues of Rhesus monkey and to assess co-localization of these proteins with OPTN.
Paraffin sections from monkey’s eyes and optic nerve were used in immunohistochemistry by immunofluorescence labeling. Control experiments were included for nonspecific staining by replacement of the primary antibodies with normal serum from the analogous species that antibody was raised from. Confocal microscope was used to visualize the slides.
Immunohistochemistry analyses revealed a prominent expression of OPTN-interacting proteins of HTT, mGluR1a, FOS, RAB8 and MYO6 in anterior segment, ciliary bodies, ciliary muscle as well as in retinal ganglion cells, inner and outer plexiforms, photoreceptor layers and optic nerve. Interestingly, excessive co-localization of these proteins with optineurin was observed in ocular tissues of Rhesus monkey. Our cDNA cloning in Rhesus monkey and homology analysis revealed that MYO6 and FOS encode for 1,253- and 380-aa polypeptides, respectively and these are 97% and 98% identical to their human counterparts. Likewise, in Silico analyses revealed that RAB8b and HTT encode for 207- and 3133-aa polypeptides, respectively and these are 100% and 95% identical to their human proteins.
Our study elucidates specific ocular expression and co-localization of Huntingtin, mGluR1a, FOS, RAB8, and Myosin 6 proteins in various ocular tissues of Rhesus monkey. It has been shown that mutant Huntingtin can cause neurodegeneration in Drosophila’s eyes. However, biological processes through which normal and abnormal copies of OPTN interact with this and other proteins still remain to be determined. Further studies are required to determine if mutations in any of these OPTN-interacting proteins will have a direct involvement in glaucoma optic neuropathy.
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