Purchase this article with an account.
J. Zhang, J. Tuo, X. Cao, D. Shen, C.-C. Chan; Synaptic Pathology of Photoreceptor Terminals in Ccl2/cx3cr1 Deficient Mice. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4136.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Although various age-related macular degeneration (AMD) mice models exhibit retinal pathologic lesions, there are limited reports about synaptic pathology in these models. Ccl2-/-/Cx3cr1-/- deficient mice develop a broad spectrum of AMD-like features. We investigate the synaptic pathology of photoreceptor terminals in the outer plexiform layer (OPL) of this mouse strain using transmission electron microscopy (EM).
Four-week-old Ccl2-/-/Cx3cr1-/- (DKO) and wide type (WT) mice (two in each group) were used for the study. Posterior part of the eyes was fixed in 2 % glutaraldehyde and 2% paraformaldehyde in 0.1 M sodium phosphate buffer. Tissues were then postfixed in 1% OsO4 for 1 hr. After rinsing and dehydration, tissues were embedded in Durcupan resin for 72 h at 60°C. 70-90 nm ultrasections were collected in 200 mesh grids and then were counterstained with 5% uranyl acetate and 0.3% lead citrate. Sections were viewed on a JEOL 1010EM. Forty photomontage images covering 5280 um2 areas of the OPL were obtained in each group. The number of photoreceptor terminals and ribbons was quantified.
Eight hundred and sixty-two and 792 photoreceptor terminals were analyzed in WT and DKO, respectively. Photoreceptor and RPE degeneration was found in DKO mice. A disorganization of the OPL was visible in DKO mice as a number of photoreceptor terminals retracted into the outer nuclear layer. Although the total number of photoreceptor terminals was similar in two groups, the number of cone pedicles was four times higher in WT than DKO (67:15, P<0.001) whereas that of rod spherules was relatively equal (795:775). Consistently, the ratio of rod spherules to cone pedicles was four times higher in DKO than WT (52:1 vs. 12:1, P<0.0001). Both ratios of ribbon terminals to non-ribbon terminals were three times higher in WT than DKO (cone pedicles: 5.0:1.0vs.1.5:1.0, P<0.05; rod spherules: 2.5:1.0 vs.0.8:1.0, P<0.0001).
Ultrastructually characteristic aberrant photoreceptor terminals and a significant decrease of cone synapses in Ccl2-/-/Cx3cr1-/- mice provide evidence, for the first time, of synaptic pathology in mouse AMD models, indicating a structural alteration for vision signal transmission and providing a new insight of vision loss in human AMD.
This PDF is available to Subscribers Only