Subtype-Specific Efficacy of Adrenoceptor Agonists in Inhibiting Lens-Induced Myopia in Chicks

PURPOSE: Alpha-adrenergic receptors (ARs) may potentially play a critical role in controlling myopia, with subtype-specific signalling pathways mediating distinct effects. This study systematically investigated the efficacy of three subtype-specific pharmacological agents in myopia control and dose-response relationships in lens-induced myopia (LIM) chick models. METHODS: White Leghorn chicks were randomised to a phosphate-buffered saline (PBS) control group or treated groups receiving metaraminol (α1-AR agonist), lofexidine (α2-AR agonist) or cirazoline (a dual α1‑AR agonist and α2‑AR antagonist) at low (3 nmol), medium (30 nmol) or high (300 nmol) doses. A -10 D single-vision lens was fitted to the right eye for 7 days to induce myopia, with intravitreal injections administered at baseline and on days 2, 4 and 6. Natural ocular recovery was allowed for another 7 days. Interocular differences (IOD) in spherical equivalent refraction (SER) and ocular biometrics were compared. RESULTS: After 7 days of lens wear, all drug groups exhibited lower myopia progression than the control group. Lofexidine showed potent and consistent myopia-inhibiting effects. The IOD in SER, vitreous chamber depth (VCD) and axial length (AL) were significantly reduced at three doses compared with PBS control (all p < 0.05). Metaraminol and cirazoline exhibited significant efficacy mainly at medium and high doses. All three α-AR modulators alleviated choroidal thinning at both 30 and 300 nmol doses. During recovery, all treatment groups trended toward emmetropia, without significant differences from the PBS group. CONCLUSIONS: This first head-to-head in vivo comparison of three subtypes of α-AR modulators in the chick LIM model demonstrates the potent myopia-suppressive effects of α2-AR agonist lofexidine at low dose. α1-AR agonist metaraminol required a distinct threshold dose to achieve efficacy and blockade of α2-AR with cirazoline may counteract anti-myopic protection. These findings provide crucial subtype-specific preclinical insights for the rational development of future drugs for myopia.