title: The role of cGMP in ocular growth and the development of form-deprivation myopia in guinea pigs.
abstract: OBJECTIVE
  Development of myopia is associated with remodeling of the sclera, a tissue composed principally of collagen. Cyclic guanosine monophosphate (cGMP) regulates collagen synthesis in several organs; therefore, we investigated the effects of soluble guanylyl cyclase (sGC) stimulation and inhibition on refraction and ocular growth in guinea pigs under normal and form-deprived (FD) conditions.
  
  
  METHODS
  Retinal and scleral cGMP concentrations were measured in normal and monocularly FD guinea pigs at 2 days, 1 week, and 2 weeks of form deprivation and following 2 days recovery. Stimulation of sGC by BAY41-2272 and inhibition by NS-2028 were achieved by daily subconjunctival injection in normal and FD eyes. Refraction and axial parameters were measured at the commencement, middle, and cessation of the experiment. cGMP levels were also determined at the end of the experiment.
  
  
  RESULTS
  Retinal and scleral cGMP concentrations increased in FD eyes from 2 days to 2 weeks (P ≤ 0.029). Levels decreased after 2 days of recovery (P ≤ 0.003). Daily injections of BAY41-2272 induced a myopic shift (P ≤ 0.001) and ocular elongation (P ≤ 0.01) in normal animals, but did not alter myopia in FD eyes (P > 0.05). In contrast, daily injections of NS-2028 partially reduced myopic shifts (P ≤ 0.012) and ocular elongation (P ≤ 0.015) induced by form deprivation, but did not affect ocular growth and refraction in normal eyes (P > 0.05). Retinal and scleral cGMP levels were increased by BAY41-2272 in normal eyes and decreased by NS-2028 in FD eyes.
  
  
  CONCLUSIONS
  Changes in cGMP signaling contribute to myopic development. Thus, cGMP may be a potential therapeutic target for preventing/treating myopia.
authors.affiliation: School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.forename: Miaozhen
authors.initials: M
authors.lastname: Pan
authors.forename: Tingting
authors.initials: T
authors.lastname: Yan
authors.forename: Yijin
authors.initials: Y
authors.lastname: Tao
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.forename: Jia
authors.initials: J
authors.lastname: Qu
authors.forename: Xiangtian
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000818:Animals; D003094:Collagen / Q000096:biosynthesis*; D003228:Conjunctiva; D006152:Cyclic GMP / Q000502:physiology*; D018450:Disease Progression; D005123:Eye / Q000254:growth & development*; D006162:Guanylate Cyclase; D006168:Guinea Pigs; D007267:Injections; D009216:Myopia / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control; D010069:Oxadiazoles / Q000494:pharmacology; D010078:Oxazines / Q000494:pharmacology; D011863:Radioimmunoassay; D012160:Retina / Q000378:metabolism; D012590:Sclera / Q000378:metabolism; D012683:Sensory Deprivation
chemical_list: C111257:NS 2028; D010069:Oxadiazoles; D010078:Oxazines; D003094:Collagen; D006162:Guanylate Cyclase; D006152:Cyclic GMP
keywords: BAY41-2272; NS-2028; cGMP; form-deprived myopia; guinea pigs