cAMP level modulates scleral collagen remodeling, a critical step in the development of myopia

PLoS One. 2013 Aug 12;8(8):e71441. doi: 10.1371/journal.pone.0071441. eCollection 2013.

Abstract

The development of myopia is associated with decreased ocular scleral collagen synthesis in humans and animal models. Collagen synthesis is, in part, under the influence of cyclic adenosine monophosphate (cAMP). We investigated the associations between cAMP, myopia development in guinea pigs, and collagen synthesis by human scleral fibroblasts (HSFs). Form-deprived myopia (FDM) was induced by unilateral masking of guinea pig eyes. Scleral cAMP levels increased selectively in the FDM eyes and returned to normal levels after unmasking and recovery. Unilateral subconjunctival treatment with the adenylyl cyclase (AC) activator forskolin resulted in a myopic shift accompanied by reduced collagen mRNA levels, but it did not affect retinal electroretinograms. The AC inhibitor SQ22536 attenuated the progression of FDM. Moreover, forskolin inhibited collagen mRNA levels and collagen secretion by HSFs. The inhibition was reversed by SQ22536. These results demonstrate a critical role of cAMP in control of myopia development. Selective regulation of cAMP to control scleral collagen synthesis may be a novel therapeutic strategy for preventing and treating myopia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colforsin / adverse effects
  • Colforsin / pharmacology
  • Collagen / genetics
  • Collagen / metabolism*
  • Cyclic AMP / metabolism*
  • Gene Expression Regulation / drug effects
  • Guinea Pigs
  • Intraocular Pressure / drug effects
  • Myopia / chemically induced
  • Myopia / genetics
  • Myopia / metabolism*
  • Retina / drug effects
  • Retina / metabolism
  • Sclera / metabolism*
  • Sensory Deprivation

Substances

  • Colforsin
  • Collagen
  • Cyclic AMP

Grants and funding

This study was supported by funding from National Basic Research Program of China (973 project, 2011CB504602 to JQ), National Natural Science Foundation of China (81271039 and 81070751 to JQ), Zhejiang Provincial Natural Science Foundation (Z2100065 to XZ), and Zhejiang Provincial Program for the Cultivation of High-level Innovative Health talents, and an Education Grant from the National Ministry (NCET-10–0977 to XZ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.