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M. R. Al-Ubaidi, D. M. Sherry, S. J. Fliesler, K. L. Moore; Protein Tyrosine-O-Sulfation Deficiency Leads to Impaired Retinal Function and Structure. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3408.
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To investigate the role(s) of protein tyrosine-O-sulfation in retinal function and structure.
Electroretinography (ERG) with correlative histologic, electron microscopic and immunohistochemical analyses were performed on wildtype mice vs. mice deficient in tyrosylprotein sulfotransferases 1 and 2 (Tpst1-/- and Tpst2-/-). SDS-PAGE and Western blot analyses of retinal extracts were performed to assess protein sulfation, using an anti-Tyr-sulfate antibody.
Multiple retinal proteins were sulfated in all species tested. Sulfated proteins were localized to photoreceptor outer segments (OS), the inner nuclear layer, and ganglion cell layer. Tpst1-/- mice initially exhibited delayed development of ERG responses; by postnatal day 50 (P50) the ERGs were normal, but by P120 mice showed reduced scotopic and photopic ERG responses with concomitant mild retinal degeneration. Tpst2-/- mice displayed early ERG deficits that, unlike Tpst1-/- mice, did not normalize with age. However, Tpst2-/- retinas appeared histologically normal. Ultrastructural studies showed that complete lack of sulfation in the double knockout (Tpst1-/-/Tpst2-/-) retina led to the formation of abnormal extensions of the disc rim into the extracellular space and continuity of the intradiscal space with the extracellular space. Furthermore, the spacing between disks was irregular and abnormally wide. Additionally, photoreceptor terminals in the double knockout retinas appeared irregular, but were able to establish ribbon synapses. Immunohistochemistry showed that disrupted protein sulfation produced cell-specific deficits in the morphology and organization of bipolar cells in particular, included an enlarged plexus of synaptotagmin 2-positive terminals in the ON sublayer of the IPL and a reduced rod bipolar cell terminal size and plexus.
These results indicate that protein sulfation is essential for proper OS morphogenesis and maintenance and affects the organization of synaptic layers.
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