GENES AND SIGNALING PATHWAYS UNDERLYING POSTNATAL AND MYOPIA DEVELOPMENT IN MOUSE SCLERA

Abstract

Atropine is more effective in reducing myopia progression than other muscarinic receptor antagonists. It was hypothesized that its effectiveness in myopia retardation comprised more pathways other than reducing muscarinic receptors. This study evaluated the hypothesis by identifying candidate genes of myopia using microarray analysis in sclera of lens-induced myopic model and normal mice and characterizing their protein expressional changes in myopic sclera before or after therapeutic intervention with atropine using western blot. I revealed that the altered expression of GABAAρ1 receptor subunits observed during myopia induction was reverted to near normal levels after atropine treatment. Furthermore, I showed that GABAAρ receptor activation promoted primary human scleral fibroblast (SF) proliferation and overexpression of GABAAρ1 receptor in SF increased GABA- and ATP-mediated calcium influx. Overall, this study suggests that atropine could retard myopia scleral development by inhibiting GABAAρ1 receptor which promotes SF proliferation and ECM remodelling via calcium-dependent mechanisms.