Abstract
Purpose: :
Activation of dopamine receptors in eye, especially in the retina, has been shown to attenuate development of form-deprivation myopia. Activation of adenosine A2A receptors are expressed in eye and have been shown to exert profound modulation on dopaminergic activity in the brain. In this study, we investigated the possible contribution of the A2A receptors to the development of myopia using adenosine A2A receptor knockout mice.
Methods: :
Congenic A2AR knockouts (in C57BL/6 background, "A2AR KO") and wild-type littermates (WT) were evaluated for biometric parameters during postnatal development (P21 to P98). These biometric measurements included corneal radius of curvature, refractive state (by an eccentric infrared photoretinoscope) and ocular dimensions including anterior chamber depth, lens thickness, and vitreous chamber depth as well as axial length (by a custom-designed optical coherence tomography which we designed).
Results: :
During postnatal development (P21 to P56), the refraction of A2AR KO mice was more myopic than that of WT littermates, with most significant difference them detected at the age of P28 (WT: 1.91 ± 6.31 D, KO: - 3.47 ± 6.10 D, p = 0.005, n = 20). Similarly, the vitreous chamber depth of homozygous mice was longer than that of WT littermates with statistical significant differences at the age of P21, P28 and P35 (P21: WT: 0.939 ± 0.031 mm, KO: 0.974 ± 0.061 mm, p = 0.034; P28: WT: 0.944 ± 0.046 mm, KO: 0.998 ± 0.048 mm, p < 0.001; P35: WT: 0.933 ± 0.031 mm, KO: 0.975 ± 0.046 mm, p = 0.003. n =20). So the refraction of A2AR KO mice was axial myopic eye. In contrast, there was no significant difference between homozygous and WT littermates at corneal radius of curvature, and lens thickness. Thus, the refraction state in A2A receptor knockout mice was similar to myopia in human and other mammilla myopia model which also showed higher myopic diopter, longer vitreous chamber depth, similar corneal radius of curvature, and lens thickness. These biometric differences cannot be attributed to the changes in body weight since there was no significant difference between the two groups during postnatal development.
Conclusions: :
The A2A receptor knockout mice developed relatively myopia during the first two months of postnatal development than WT littermates, but return to normal development as WT littermates thereafter. Thus, adenosine A2A receptor in retina may be involved in the visual-induced ocular growth and the development of refraction.
Keywords: myopia • adenosine