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X. Zhou, Q. Huang, J. An, R. Lu, L. Jiang, J. Chen, J. Qu; The Relative Myopia in Mice Deficient in Adenosine A2a Receptors Is Associated With the Reduced Collagen Synthesis in Sclera. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3839.
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© ARVO (1962-2015); The Authors (2016-present)
We recently reported that the A2A receptor knockout mice confer a relatively myopia during the first two months of postnatal development. To investigate the molecular basis for this relative myopia, we determined collagen fibril diamters in sclera of A2A receptor knockout mice and collagen synthesis in cultured human scerla fibroblasts.
Congenic A2AR knockouts (in C57BL/6 background, "A2AR KO") and wild-type littermates (WT) were evaluated for scleral collagen fibril diameter at postnatal day 35 by electron microscope. Furthermore, the effect of pharmacological activation of A2ARs on the mRNA levels for Collagen I, III and V in cultured human scleral fibroblasts were determined by real time PCR.
Ultrastructural analyses revealed that the mean cross-sectional diameters of collagen fibrils from posterior scleral regions collagen of A2AR KO mice were significantly samller than that of WT mice (WT: 69.78±9.20 nm, KO: 59.32±11.87 nm, p=0.009). Consequently, the density of the sclera fibrils in A2AR KO mice (173.31 ±42.26/mm2) were significantly denser than that of WT littermates (141.72 ± 34.19/mm2) ( P=0.02). Consistent with the finding of reduced collagen fibrils by genetic inactivation of the A2AR, activation of the A2AR by the A2A R agonist CGS21680 increased the mRNA levels for collagen I, III and V mRNA in a dose-dependent fashion in culture human sclera fibroblast. CGS21680 (1 µM) significantly increased the mRNA levels for collagen I, III and V compared to the vehicle (P<0.01, one-way ANOVA). This CGS21680-induced increase in the mRNA levels for collagen I, III and V was reversed by the co-administration of the A2AR antagonist SCH58261 (1 µM.) (P<0.01, one-way ANOVA), indicating the A2AR specificity of CGS21680 effect.
Reduced collagen fibril diameter in sclera of A2AR KO and increased expression of collagen expression in the sclera fibroblasts suggest that adenosine A2A receptor may control the visual-induced ocular growth and the development of myopia through modulation of collagen synthesis in the sclera.
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