title: Upregulation of regulator of G-protein signaling 2 in the sclera of a form deprivation myopic animal model.
abstract: OBJECTIVE
  Scleral remodeling is an important mechanism underlying the development of myopia. Atropine, an antagonist of G protein-coupled muscarinic receptors, is currently used as an off-label treatment for myopia. Regulator of G-protein signaling 2 (RGS2) functions as an intracellular selective inhibitor of muscarinic receptors. In this study we measured scleral RGS2 expression and scleral remodeling in an animal model of myopia in the presence or absence of atropine treatment.
  
  
  METHODS
  GUINEA PIGS WERE ASSIGNED TO FOUR GROUPS: normal (free of form deprivation), form deprivation myopia (FDM) for 4 weeks, FDM treated with saline, and FDM treated with atropine. Biometric measurements were then performed. RGS2 expression levels and scleral remodeling, including scleral thickness and collagen type I expression, were compared among the four groups.
  
  
  RESULTS
  Compared with normal eyes and contralateral control eyes, the FDM eyes had the most prominent changes in refraction, axial length, and scleral remodeling, indicating myopia. There was no significant difference between control and normal eyes. Hematoxylin and eosin staining showed that the scleral thickness was significantly thinner in the posterior pole region of FDM eyes compared to normal eyes. Real-time PCR and western blot analysis showed a significant decrease in posterior scleral collagen type I mRNA and protein expression in the FDM eyes compared to the normal eyes. The FDM eyes also had increased levels of RGS2 mRNA and protein expression in the sclera. Atropine treatment attenuated the FDM-induced changes in refraction, axial length, and scleral remodeling. Interestingly, atropine treatment significantly increased collagen type I mRNA expression but decreased RGS2 mRNA and protein expression in the sclera of the FDM eyes.
  
  
  CONCLUSIONS
  We identified a significant RGS2 upregulation and collagen type I downregulation in the sclera of FDM eyes, which could be partially attenuated by atropine treatment. Our data suggest that targeting dysregulated RGS2 may provide a novel strategy for development of therapeutic agents to suppress myopia progression.
authors.affiliation: Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai,China ; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, China ; Key Laboratory of Myopia, Ministry of Health PR China, Shanghai, China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Zou
authors.affiliation: Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai,China ; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, China ; Key Laboratory of Myopia, Ministry of Health PR China, Shanghai, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai,China ; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, China ; Key Laboratory of Myopia, Ministry of Health PR China, Shanghai, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai,China ; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, China ; Key Laboratory of Myopia, Ministry of Health PR China, Shanghai, China.
authors.forename: Renyuan
authors.initials: R
authors.lastname: Chu
authors.affiliation: Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai,China ; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, China ; Key Laboratory of Myopia, Ministry of Health PR China, Shanghai, China.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai,China ; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, China ; Key Laboratory of Myopia, Ministry of Health PR China, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai,China ; Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, China ; Key Laboratory of Myopia, Ministry of Health PR China, Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology / Q000627:therapeutic use; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D006168:Guinea Pigs; D009216:Myopia / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype; D020710:RGS Proteins / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D012590:Sclera / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012683:Sensory Deprivation; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*
chemical_list: D024042:Collagen Type I; D020710:RGS Proteins; D001285:Atropine