Genetic deletion of the adenosine A2A receptor confers postnatal development of relative myopia in mice.
OBJECTIVE
To critically evaluate whether the adenosine A2A receptor (A2AR) 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 A2AR 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 A2AR 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 A2AR 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 A2AR KO mice was associated with ultrastructural changes in the sclera: Electron microscopy revealed denser collagen fibrils with reduced diameter in A2AR KO compared with WT. Last, A2AR 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 A2AR promotes development of relative myopia with increased axial length and altered scleral collagen fiber structure during postnatal development in mice. Thus, the A2AR may be important in normal refractive development.
Zhou
Xiangtian
X
School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical College, Wenzhou, China.
Huang
Qinzhu
Q
An
Jianhong
J
Lu
Runxia
R
Qin
Xiaoyi
X
Jiang
Liqin
L
Li
Yuan
Y
Wang
Jianhua
J
Chen
Jiangfan
J
Qu
Jia
J
D000818:Animals; D000869:Anterior Eye Segment / Q000254:growth & development* / Q000473:pathology / Q000502:physiology; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D024062:Collagen Type V / Q000235:genetics / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009216:Myopia / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000235:genetics* / Q000378:metabolism; D012029:Refraction, Ocular / Q000502:physiology*; D012590:Sclera / Q000254:growth & development / Q000473:pathology / Q000648:ultrastructure; D012995:Solubility
D024042:Collagen Type I; D024061:Collagen Type III; D024062:Collagen Type V; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A