Genetic Deletion of the Adenosine A2A Receptor Confers Postnatal Development of Relative Myopia in Mice

PURPOSE. To critically evaluate whether the adenosine A(2A) receptor (A(2A) R) plays a role in postnatal refractive development in mice. METHODS. Custom-built biometric systems specifically designed for mice were used to assess the development of relative myopia by examining refraction and biometrics in A(2A)R knockout (KO) mice and wild-type (WT) littermates between postnatal days (P) 28 and P56. Ocular dimensions were measured by customized optical coherence tomography (OCT), refractive state by eccentric infrared photorefraction (EIR), and corneal radius of curvature by modified keratometry. Scleral collagen diameter and density were examined by electron microscopy on P35. The effect of A(2A)R activation on collagen mRNA expression and on soluble collagen production was examined in cultured human scleral fibroblasts by real-time RT-PCR and a collagen assay kit. RESULTS. Compared with WT littermates, the A(2AR) KO mice displayed relative myopia (average difference, 5.1 D between P28 and P35) and associated increases in VC depth and axial length from P28 to P56. Furthermore, the myopic shift in A(2A)R KO mice was associated with ultrastructural changes in the sclera: Electron microscopy revealed denser collagen fibrils with reduced diameter in A(2A)R KO compared with WT. Last, A(2A)R activation induced expression of mRNAs for collagens I, III, and V and increased production of soluble collagen in cultured human scleral fibroblasts. CONCLUSIONS. Genetic deletion of the A(2A)R promotes development of relative myopia with increased axial length and altered scleral collagen fiber structure during postnatal development in mice. Thus, the A(2A)R may be important in normal refractive development. (Invest Ophthalmol Vis Sci. 2010;51:4362-4370) DOI:10.1167/iovs.09-3998