褚仁远   钱宜珊

复旦大学附属眼耳鼻喉科医院   200031

Purpose:To investigate whether Sonic hedgehog(Shh)plays a role in postnatal eye development and the development of experimentally induced myopia.

Method:Expression of Shh，Patched-1(Ptc-1)，and Gli3 was evaluated in the eyes of 13-to 14-day old C57B/L6 mice with form-deprivation myopia(FDM)(n=100)and controls(n=100)using real-time PCR and western blot analysis.In a second experiment，336 mice were divided into two groups：the first wore a unilateral translucent diffuser to induce myopia and the second served as a control.Both groups received four intravitreal injections of either Shh-N(Sonic hedgehog amino-terminal peptide)or cyclopamine(a specific inhibitor of the Shh pathway)every other day.Retinoscopic refraction and axial length measurements were performed on the 11thday of form-deprivation.Sections of the eyes were observed using a light microscope.

Results:Inducing myopia caused a significant increase in expression of Shh mRNA(7 days：t=6.09，P=0.004；14 days：t=3.48，P=0.025)and protein(7 days：t=4.06，P=0.015；14 days：t=4.25，P=0.013).Expression of both Gli3 mRNA(t=7.61，P=0.002)and protein(t=2.89，P=0.045)increased after 7 days of occlusion.Administration of Shh-N stimulated the development of myopia and axial growth in both occluded(refraction：F=7.49，P=0.001；axial length：F=9.89，P<0.001)and non-occluded eyes(refraction：F=14.20，P<0.001；axial length：F=20.37，P<0.001).Cyclopamine reduced myopic refractive error and axial elongation in occluded eyes(refraction：F=27.91，P<0.001；axial length：F=15.18，P<0.001).It also influenced non-occluded eyes，reducing axial growth and shifting the refraction toward hyperopia(refraction：F=14.81，P<0.001；axial length：F=3.99，P=0.024).No difference in retinal thickness was found between experimental and control eyes.

Conclusions:The Shh-signaling pathway may influence both form-deprivation myopia and the postnatal growth of eyes with normal visual input.Key words：Sonic hedgehog；form-deprivation myopia；retina；cyclopamine