Abstract
Purpose :
Atropine, a non-selective muscarinic receptor antagonist, is often used as a treatment for common childhood myopia, but it is unclear whether it is useful for the treatment of syndromic myopia. Here, we evaluate the effect of atropine on the regulation of eye growth in mice with a Foxg1-conditional knockout of low-density lipoprotein receptor-related protein 2 (Lrp2), which causes Donnai-Barrow syndrome characterized by extremely high myopia in humans.
Methods :
Male (M) and female (F) C57BL/6 mice homozygous for both FoxG1cre and Lrp2fl (M n=9; F n=7) and littermates negative for FoxG1cre (M n=7; F n=4) were housed under full-spectrum 200 lux illumination (18h day/6h night). From postnatal day (P) 30 to 56, left eyes received one droplet 1% atropine sulfate daily, while right eyes received saline. Ocular biometry including axial length was measured using SD-OCT in anesthetized mice at P28, P30, P42 and P56.
Results :
At P28, KO mice had significantly larger axial length (AL), compared to littermate controls (means±SEM KO M: 3269±38, Ctr M: 3166±19; KO F: 3262±50, Ctr F: 3102±30 µm; both M and F, p<0.05, unpaired t-tests). Atropine reduced AL growth significantly in both KO and Ctr mice (dAL, atropine minus saline treatment: KO M: -26±9; Ctr M: -42±7; KO F: -55±8; Ctr F: -62±4 µm, p<0.01 for treatment, MANOVA), which was mainly caused by a reduction of anterior chamber depth growth (KO M: -54±6; Ctr M: -42±6; KO F: -51±3; Ctr F: -47±3, p<<0.0001 for treatment, MANOVA). Lens thickness and vitreous chamber depth were not significantly affected by atropine.
Conclusions :
Atropine reduced axial elongation in a mouse model lacking Lrp2, a protein which is directly implicated in controlling growth cues of the eye. This suggests that the mechanism of action of atropine is robust and that this treatment could be beneficial in humans with a syndromic cause of myopia.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.