Limits...
Experimental murine myopia induces collagen type Iα1 (COL1A1) DNA methylation and altered COL1A1 messenger RNA expression in sclera.

Zhou X, Ji F, An J, Zhao F, Shi F, Huang F, Li Y, Jiao S, Yan D, Chen X, Chen J, Qu J - Mol. Vis. (2012)

Bottom Line: MD was found to induce myopia in the treated eyes.Consistent with the CpG methylation, scleral COL1A1 mRNA was reduced by 57% in the MD-treated eyes compared to normal controls (p<0.05).After seven days of MD recovery, CpG methylation was significantly reduced (p=0.01).

View Article: PubMed Central - PubMed

Affiliation: School of Optometry & Ophthalmology and Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China.

ABSTRACT

Purpose: To investigate whether myopia development is associated with changes of scleral DNA methylation in cytosine-phosphate-guanine (CpG) sites in the collagen 1A1 (COL1A1) promoter and messenger RNA (mRNA) levels following murine form deprivation myopia.

Methods: Fifty-seven C57BL/6 mice (postnatal day 23) were randomly assigned to four groups: (1) monocular form deprivation (MD) in which a diffuser lens was placed over one eye for 28 days; (2) normal controls without MD; (3) MD recovery in which the diffuser lens was removed for seven days; and (4) MD recovery normal controls. The DNA methylation pattern in COL1A1 promoter and exon 1 was determined by bisulfite DNA sequencing, and the COL1A1 mRNA level in sclera was determined by quantitative PCR.

Results: MD was found to induce myopia in the treated eyes. Six CpG sites in the promoter and exon 1 region of COL1A1 were methylated with significantly higher frequency in the treated eyes than normal control eyes (p<0.05), with CpG island methylation in MD-contralateral eyes being intermediate. Consistent with the CpG methylation, scleral COL1A1 mRNA was reduced by 57% in the MD-treated eyes compared to normal controls (p<0.05). After seven days of MD recovery, CpG methylation was significantly reduced (p=0.01). The methylation patterns returned to near normal level in five CpG sites, but the sixth was hypomethylated compared to normal controls.

Conclusions: In parallel with the development of myopia and the reduced COL1A1 mRNA, the frequency of methylation in CpG sites of the COL1A1 promoter/exon 1 increased during MD and returned to near normal during recovery. Thus, hypermethylation of CpG sites in the promoter/exon 1 of COL1A1 may underlie reduced collagen synthesis at the transcriptional level in myopic scleras.

Show MeSH

Related in: MedlinePlus

Methylation percentages of cytosine-phosphate-guanine (CpG) sites in the collagen type Iα1 promoter region in scleras of monocular deprivation and control eyes after four weeks of monocular deprivation and one week of recovery. Numbers in parentheses on the x-axis are the locations of the cytosine-phosphate-guanine (CpG) sites. Methylation at site 11 was significantly less in the monocular deprivation–recovery (MD-R) eyes than in the NC58 eyes. MD-R: after 7 days of recovery following 4 weeks of monocular deprivation, MD-RC: contralateral control eyes, NC58: age-matched normal control eyes for MD recovery, *, p<0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3369898&req=5

f5: Methylation percentages of cytosine-phosphate-guanine (CpG) sites in the collagen type Iα1 promoter region in scleras of monocular deprivation and control eyes after four weeks of monocular deprivation and one week of recovery. Numbers in parentheses on the x-axis are the locations of the cytosine-phosphate-guanine (CpG) sites. Methylation at site 11 was significantly less in the monocular deprivation–recovery (MD-R) eyes than in the NC58 eyes. MD-R: after 7 days of recovery following 4 weeks of monocular deprivation, MD-RC: contralateral control eyes, NC58: age-matched normal control eyes for MD recovery, *, p<0.05.

Mentions: In the MD-R eyes, the methylation percentages of the six CpG sites that were previously elevated (1, 3, 9, 14, 18, and 19) were similar to those of the MD-RC and NC58 eyes (Figure 5). Thus, the recovery from myopia was associated with a loss of DNA methylation at the CpG sites. The methylation percentage of CpG site 11 in the MD-R eyes was reduced significantly compared to the NC58 eyes (Figure 5).


Experimental murine myopia induces collagen type Iα1 (COL1A1) DNA methylation and altered COL1A1 messenger RNA expression in sclera.

Zhou X, Ji F, An J, Zhao F, Shi F, Huang F, Li Y, Jiao S, Yan D, Chen X, Chen J, Qu J - Mol. Vis. (2012)

Methylation percentages of cytosine-phosphate-guanine (CpG) sites in the collagen type Iα1 promoter region in scleras of monocular deprivation and control eyes after four weeks of monocular deprivation and one week of recovery. Numbers in parentheses on the x-axis are the locations of the cytosine-phosphate-guanine (CpG) sites. Methylation at site 11 was significantly less in the monocular deprivation–recovery (MD-R) eyes than in the NC58 eyes. MD-R: after 7 days of recovery following 4 weeks of monocular deprivation, MD-RC: contralateral control eyes, NC58: age-matched normal control eyes for MD recovery, *, p<0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3369898&req=5

f5: Methylation percentages of cytosine-phosphate-guanine (CpG) sites in the collagen type Iα1 promoter region in scleras of monocular deprivation and control eyes after four weeks of monocular deprivation and one week of recovery. Numbers in parentheses on the x-axis are the locations of the cytosine-phosphate-guanine (CpG) sites. Methylation at site 11 was significantly less in the monocular deprivation–recovery (MD-R) eyes than in the NC58 eyes. MD-R: after 7 days of recovery following 4 weeks of monocular deprivation, MD-RC: contralateral control eyes, NC58: age-matched normal control eyes for MD recovery, *, p<0.05.
Mentions: In the MD-R eyes, the methylation percentages of the six CpG sites that were previously elevated (1, 3, 9, 14, 18, and 19) were similar to those of the MD-RC and NC58 eyes (Figure 5). Thus, the recovery from myopia was associated with a loss of DNA methylation at the CpG sites. The methylation percentage of CpG site 11 in the MD-R eyes was reduced significantly compared to the NC58 eyes (Figure 5).

Bottom Line: MD was found to induce myopia in the treated eyes.Consistent with the CpG methylation, scleral COL1A1 mRNA was reduced by 57% in the MD-treated eyes compared to normal controls (p<0.05).After seven days of MD recovery, CpG methylation was significantly reduced (p=0.01).

View Article: PubMed Central - PubMed

Affiliation: School of Optometry & Ophthalmology and Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China.

ABSTRACT

Purpose: To investigate whether myopia development is associated with changes of scleral DNA methylation in cytosine-phosphate-guanine (CpG) sites in the collagen 1A1 (COL1A1) promoter and messenger RNA (mRNA) levels following murine form deprivation myopia.

Methods: Fifty-seven C57BL/6 mice (postnatal day 23) were randomly assigned to four groups: (1) monocular form deprivation (MD) in which a diffuser lens was placed over one eye for 28 days; (2) normal controls without MD; (3) MD recovery in which the diffuser lens was removed for seven days; and (4) MD recovery normal controls. The DNA methylation pattern in COL1A1 promoter and exon 1 was determined by bisulfite DNA sequencing, and the COL1A1 mRNA level in sclera was determined by quantitative PCR.

Results: MD was found to induce myopia in the treated eyes. Six CpG sites in the promoter and exon 1 region of COL1A1 were methylated with significantly higher frequency in the treated eyes than normal control eyes (p<0.05), with CpG island methylation in MD-contralateral eyes being intermediate. Consistent with the CpG methylation, scleral COL1A1 mRNA was reduced by 57% in the MD-treated eyes compared to normal controls (p<0.05). After seven days of MD recovery, CpG methylation was significantly reduced (p=0.01). The methylation patterns returned to near normal level in five CpG sites, but the sixth was hypomethylated compared to normal controls.

Conclusions: In parallel with the development of myopia and the reduced COL1A1 mRNA, the frequency of methylation in CpG sites of the COL1A1 promoter/exon 1 increased during MD and returned to near normal during recovery. Thus, hypermethylation of CpG sites in the promoter/exon 1 of COL1A1 may underlie reduced collagen synthesis at the transcriptional level in myopic scleras.

Show MeSH
Related in: MedlinePlus