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syeda farina asghar, William K Stell; Atropine for Myopia: Muscarinic and Non-Muscarinic Effects in Chick. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1135.
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© ARVO (1962-2015); The Authors (2016-present)
There is a worldwide epidemic of myopia. The best available treatment is topical atropine (ATRO), which is usually assumed to act at specific muscarinic receptors (mAChR); but experiments in chicks cast doubt on this assumption. ATRO is a racemic mixture of enantiomers, only one of which, L-hyoscyamine (L-HYO), is selective for mAChRs. Here we used L-HYO as a selective tool to identify inhibitory action(s) mediated by mAChRs in form-deprivation myopia (FDM).
One-day-old (P1) chicks (Gallus gallus domesticus) were housed at 25 o C, on a 12:12-hour Lt:Dk cycle (light on at 06:00). The 5-day treatment protocol (3 independent trials, 4 treatments/trial, total n=16-18 chicks/treatment) was as follows: Day one (D1), attach diffusers over right (R) eyes; D2 & D4, inject ATRO (0.24nmol) or L-HYO (0.12 or 1.2 nmol), in 20 µL vehicle (VEH: 5% ethanol-saline), intravitreally into R eyes, and VEH alone into left (L) eyes; D5, refract eyes without cycloplegia, euthanize, remove eyes, measure eye size (with digital calipers) and weight.
Results are expressed as mean interocular difference (Treated-Control, R-L) ± SD, after verifying absence of treatment effects in non-goggled eyes. Statistics: One-way ANOVA + Tukey’s or Dunn’s post-test, after verifying normal distribution. ATRO (0.24nmol) significantly inhibited the FD-induced increases in dRE (VEH: -4.44±1.50D; ATRO: -1.17±0.86D; p>0.0001), dAL (VEH: 0.35±0.11mm; ATRO: 0.22±0.12mm; p=0.004), and dEqD (VEH: 0.40±0.14mm; ATRO: 0.28±0.14mm; p=0.006). L-HYO, in contrast, inhibited only dRE, at both the equivalent dose (0.12nmol: -1.75±1.00D; p>0.0001) and the 10x higher dose (1.2nmol: -1.35±0.86D; p>0.0001). No other statistically significant treatment effects were observed (p<0.05).
L-HYO, the mAChR-preferring enantiomer in racemic ATRO, inhibited the myopic refractive error (dRE) but not the ocular enlargement (dAL, dEqD, dWW) of FDM. This result is consistent with muscarinic regulation of choroidal thickness, as suggested by Nickla et al. (OPO’13). The effects of ATRO on the other indicators of eye growth suggest that they are due to activation of non-muscarinic effectors, e.g., by adrenergic receptors (Carr et al., IOVS’18, CEO’19; Liu et al. MolVis’17). Identifying the receptor(s) responsible for such mAChR-independent effects of ATRO should be useful for developing more specific and effective anti-myopia drugs.
This is a 2020 ARVO Annual Meeting abstract.
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