Rod Photoreceptor Ribbon Synapses in DBA/2J Mice Show Progressive Age-Related Structural Changes

Abstract

The DBA/2J mouse is a commonly used animal model in glaucoma research. The eyes of DBA/2J mice show severe age-related changes that finally lead to the degeneration of retinal ganglion cells and the optic nerve. Recent electroretinogram studies identified functional deficits, which suggest that also photoreceptor cells are involved in the pathological processes occurring in the DBA/2J mouse retina. In a comparative study, we examined anatomical and molecular changes in the retinae of DBA/2J and C57BL/6 control mice with light and electron microscopy and with PCR analyses. In the retina of the DBA/2J mouse, we found a thinning of the outer plexiform layer, the first synaptic layer in the transfer of visual signals, and age-dependent and progressive degenerative structural changes at rod photoreceptor ribbon synapses. The structural ribbon changes represent a photoreceptor synaptic phenotype that has not yet been described in this animal model of secondary angle-closure glaucoma. Furthermore, genes of the classical complement cascade were upregulated in the photoreceptor cells of aging DBA/2J mice, suggesting a putative link between ribbon synapse degradation and the innate immune system.

Retinal neurodegeneration in experimental glaucoma

“…Our results are in agreement with previous reports showing that OHT also results in adverse effects on the cone photoreceptor population: (i) in rodent models analyzed with morphometric techniques (Abbott et al, 2014;Fernández-Sánchez et al, 2014;Fuchs et al, 2012;Guo et al, 2010;Rojas et al, 2014), with functional techniques (Chen et al, 2015;Georgiou et al, 2014;Heiduschka et al, 2010;Mittag et al, 2000;Pérez de Lara et al, 2014), or with both Topological analysis of RGCs, L-cones, and S-cones 3 months after OHT. Isodensity maps showing topological distributions of entire populations of retinal ganglion cells (RGCs), L-cones, or S-cones in the same retinas.…”

Cellular responses following retinal injuries and therapeutic approaches for neurodegenerative diseases

“…The retraction of rod photoreceptor synapses is also evident in retinal detachment and RP (Fariss et al, 2000). In DBA/2J mice models of ocular hypertension it has been documented an alteration of rod photoreceptor ribbon structure Fuchs et al, 2012). Similar results were found in transgenic mice overexpressing the guanylate cyclase activating protein 2 (GCAP2) in rods leading to a shortening of synaptic ribbons, and to a higher than normal percentage of club-shaped and spherical ribbon morphologies (Lopez-del Hoyo et al, 2012).…”

Functional architecture of the retina: Development and disease

“…In particular, reduction of OPL thickness and number of photoreceptor ribbons has been reported in mice after intraocular pressure elevation (Cuenca et al, 2010). Ultrastructural alterations of photoreceptor ribbons such as the appearance of club-shaped or detached spherical ribbons have been observed in DBA/2J glaucoma model mice (Fuchs et al, 2012). These findings underscore the notion that changes in connectivity are not restricted to the GCL where cell death is occurring.…”