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Michael Scholz, Michaela Fuchs, Jenny Atorf, Ralf Enz, Johann H. Brandstatter; Degenerative Changes At The Rod Photoreceptor Synaptic Ribbon In Aging Dba2/j Mice. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6440.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the phenotype of photoreceptor synapses in the aging DBA2/J retina and to correlate them with changes in retinal layer architecture. To show first data suggesting a correlation between the synaptic phenotype and an upregulation of C1q in the DBA2/J retina.
The retinae of C57Bl/6 (B6) and DBA2/J (D2J) mice at the ages of 2, 6 and 10 months were investigated for changes in retinal layer morphology and in photoreceptor synaptic terminals within the Outer plexiform layer (OPL). Thickness quantifications of retinal layers were analyzed on histological sagittal eye sections. Ultrastructural analysis was performed to detect and quantify different ribbon morphologies in rod photoreceptor synaptic terminals of BL6 and D2J mice. Outer nuclear layer and inner segments of photoreceptor cells of retinae of both strains were cut by laser capture microdissection. RT-PCR on cDNA preparations of these tissues was performed to detect differences in C1q regulation.
In BL6 mice, the ratios of different ribbon morphologies within the photoreceptor synaptic terminals were similar and showed no age-related effects. In 2 months old D2J mice, fewer ribbons were rod-shaped than in BL6 mice of the same age (66.6%) while more ribbons were club-shaped (28.1%). The amount of spherical-shaped ribbons was not changed (5.3%). In 6 months old D2J mice, the ratio of rod-shaped and club-shaped ribbons decreased slightly and more spherical-shaped ribbons were observed (18.4%). This was even more obvious in 10 months old D2J mice with 37.9% of spherical-shaped ribbons. This corresponds to a 7-fold increase in spherical-shaped ribbons in D2J mice from 2 to 10 months of age. At the age of 10 months, the OPL thickness in D2J retinae was significantly diminished in comparison to 2 (p<0.05) and 6 (p<0.01) months old animals. Comparing the expression of C1qA in the ONL of 2 and 6 months old mice showed a significant upregulation in D2J animals, but not in BL6. At 10 months, only C1qC showed a significant upregulation when compared to 2 months old D2J retinae.
Spherical-shaped ribbons are usually found as ribbon precursors in the developing retina, but have also been described as products of ribbon degradation. The structural changes in D2J photoreceptor terminals also correlate well with a reduced OPL thickness in these mice. Despite the pathological processes in their terminals, we did not find a reduced number of photoreceptor cells in the examined D2J retinae. Thus, photoreceptors do not seem to degenerate even when synaptic ribbons are disturbed. We provide first experimental data suggesting a correlation between the synaptic phenotype and an upregulation of the complement factor C1q in photoreceptors of the aging D2J retina.
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