APLP2 Regulates Refractive Error and Myopia Development in Mice and Humans
(A) Effect of targeted deletion of Aplp2 on refractive eye development in the mouse. Aplp2 knockout mice (generated on C57BL/6J background) develop high degrees of hyperopia (+11.5 ± 2.2 D, p < 1.0 × 10−4) compared to both heterozygous (-0.8 ± 2.0 D, p < 1.0 × 10−4) and wild-type (+0.3 ± 2.2 D, p < 1.0 × 10−4) littermates. Refractive errors were measured at P35 (age when refractive errors stabilize in mice) using automated infrared photorefractor. Red horizontal bars, mean. (B) Effect of targeted deletion of Aplp2 on susceptibility to experimental myopia in mice. Lack of Aplp2 expression had a negative dose-dependent effect on susceptibility to myopia in mice. Visual form deprivation (VFD) induced -1.2 ± 0.6 D of myopia (p = 3.0 × 10−2) in the Aplp2 knockouts compared to -5.7 ± 1.1 D (p < 1.0 × 10−4) in heterozygous and -11.0 ± 1.7 D (p < 1.0 × 10−4) in wild-type littermates. VFD was carried out for 21 days from P24 through P45 and refractive status of the deprived eyes versus control eyes was measured using an automated infrared photorefractor (Methods). Red horizontal bars, mean. (C) Effect of targeted deletion of Aplp2 on visual acuity in mice. Visual acuity in Aplp2 knockouts was not significantly different from that in the heterozygous and wild-type littermates (F(2, 20) = 0.6, p = 0.58). Error bars, s.d.; n = 13. (D) Effect of targeted deletion of Aplp2 on contrast sensitivity in mice. Lack of Aplp2 resulted in a dose-dependent reduction in contrast sensitivity (F(12, 120) = 3.6, p = 1.5 × 10−4). Error bars, s.d.; n = 13. Both visual acuity and contrast sensitivity were measured at P80 using a mouse virtual optomotor system.