cAMP level modulates scleral collagen remodeling, a critical step in the development of myopia.
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.
School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China.
Yijin
Y
Tao
Miaozhen
M
Pan
Shufeng
S
Liu
Fang
F
Fang
Runxia
R
Lu
Chanyi
C
Lu
Min
M
Zheng
Jianhong
J
An
Hongjia
H
Xu
Fuxin
F
Zhao
Jiang-Fan
JF
Chen
Jia
J
Qu
Xiangtian
X
Zhou
D000818:Animals; D005576:Colforsin / Q000009:adverse effects / Q000494:pharmacology; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006168:Guinea Pigs; D007429:Intraocular Pressure / Q000187:drug effects; D009216:Myopia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D012590:Sclera / Q000378:metabolism*; D012683:Sensory Deprivation
D005576:Colforsin; D003094:Collagen; D000242:Cyclic AMP