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Inhibition of Retinal AdoRA2a Activity Attenuates Myopia Progression.
Shengcong Liu1,2,3, Zhenqi Guan1,2,3, Xingxing Yang1,2,3
1Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Eye Hospital, Wenzhou Medical University, Wenzhou, China.
Investigative Ophthalmology & Visual Science
|January 14, 2026
Summary
Retinal adenosine A2a receptors (AdoRA2a) are key regulators of myopia progression. Inhibiting AdoRA2a in mice significantly reduced myopia, suggesting potential therapeutic strategies for this eye condition.
Area of Science:
- Ophthalmology
- Neuroscience
- Pharmacology
Background:
- Myopia, or nearsightedness, is a growing global health concern.
- Adenosine receptors (AdoRs) are implicated in myopia, but the specific subtype and tissue remain unidentified.
- 7-methylxanthine, a nonselective AdoR antagonist, shows potential in suppressing myopia.
Purpose of the Study:
- To investigate the role of the adenosine receptor A2a subtype (AdoRA2a) in regulating myopia progression.
- To determine if the retina is the critical site for AdoRA2a's action in myopia.
Main Methods:
- Monocular form deprivation myopia (FDM) was induced in mice.
- Retinal adenosine levels and CD39/CD73 expression were measured.
- Retina-specific AdoRA2a knockout mice and wild-type littermates were used.
- Mice received vehicle or the selective AdoRA2a antagonist KW6002.
- Dopamine D2 receptor knockout (Drd2-CKO) mice were also studied.
Main Results:
- FDM increased retinal adenosine and CD39/CD73 expression.
- AdoRA2a inhibition (knockout or KW6002) attenuated FDM progression.
- Normal refractive development was unaffected by AdoRA2a inhibition.
- AdoRA2a and dopamine D2 receptors (Drd2) colocalized in the retina.
- KW6002 lacked effect in Drd2-CKO mice, suggesting an interaction.
Conclusions:
- Retinal AdoRA2a plays a critical role in myopia progression.
- The retina is the key site for AdoRA2a's effects on myopia.
- An AdoRA2a-Drd2 interaction mechanism is proposed.
- KW6002 shows potential as a therapeutic agent for myopia.
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