title: The sonic hedgehog signaling pathway induces myopic development by activating matrix metalloproteinase (MMP)-2 in Guinea pigs.
abstract: OBJECTIVE
  To investigate whether the Sonic hedgehog (Shh) signaling induces myopic development by increasing the expression of matrix metalloproteinase (MMP)-2 in guinea pigs.
  
  
  METHODS
  A translucent diffuser was glued onto the right eye to induce form-deprivation myopia (FDM) in 10 guinea pigs. Four guinea pigs were served as a control group. The other 100 guinea pigs were subdivided into 5 groups (20 per group) and received a 10 µl intravitreal injection every 2 days for 4 times. Two groups were injected with 20 or 50 µg/ml Shh amino-terminal peptide (Shh-N) into the right eye and 0.1% bovine serum albumin into the other. FDM was induced in the right eyes of the three cyclopamine-treated groups and both eyes were injected with 50, 100, or 200 µg/ml cyclopamine. Retinoscopic refraction and eye dimensions were assessed on Day 14 of treatment. MMP-2 protein expression was determined in both scleras by western blotting.
  
  
  RESULTS
  Both concentrations of Shh-N stimulated myopic development and axial growth as compared with control eyes. Myopia and axial elongation were significantly greater in the 50 µg/ml than in the 20 µg/ml Shh-N group (P<0.001 and P = 0.0019, respectively). All three doses of cyclopamine significantly attenuated myopic development compared with the FDM group (P<0.0001). Cyclopamine at 100 or 200 µg/ml significantly reduced axial elongation compared with the FDM group (P = 0.044 and P = 0.001, respectively). FDM-induced myopia and axial elongation were significantly greater in the 50 µg/ml than in the 200 µg/ml cyclopamine group (P<0.0001 and P = 0.008, respectively). MMP-2 expression was significantly greater in Shh-N-treated eyes than in the control eyes, and was lower in the cyclopamine plus FDM groups than in the FDM group.
  
  
  CONCLUSIONS
  The Shh signaling pathway induces myopic development by activating MMP-2 in guinea pigs.
authors.affiliation: Department of Ophthalmology, EENT Hospital, Fudan University, Shanghai, China; Key Laboratory of Myopia, Ministry of Health, Shanghai, China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, EENT Hospital, Fudan University, Shanghai, China; Key Laboratory of Myopia, Ministry of Health, Shanghai, China.
authors.forename: Yishan
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Department of Ophthalmology, EENT Hospital, Fudan University, Shanghai, China; Key Laboratory of Myopia, Ministry of Health, Shanghai, China.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Ophthalmology, EENT Hospital, Fudan University, Shanghai, China; Key Laboratory of Myopia, Ministry of Health, Shanghai, China.
authors.forename: Renyuan
authors.initials: R
authors.lastname: Chu
mesh_terms: D000818:Animals; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D006168:Guinea Pigs; D053823:Hedgehog Proteins / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009216:Myopia / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D012029:Refraction, Ocular / Q000187:drug effects; D012160:Retina / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D012590:Sclera / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects; D014704:Veratrum Alkaloids / Q000494:pharmacology
chemical_list: D053823:Hedgehog Proteins; D014704:Veratrum Alkaloids; D020778:Matrix Metalloproteinase 2; C000541:cyclopamine