HOXA9 is a novel myopia risk gene
Abstract Purpose A recent meta-analysis revealed PAX6 as a risk gene for myopia. There is a link between PAX6 and HOXA9. Furthermore, HOXA9 has been reported to activate TGF-β that is a risk factor for myopia. We speculate HOXA9 may participate in myopia development. Methods The Singapore GUSTO birt...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-01-01
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| Series: | BMC Ophthalmology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12886-019-1038-9 |
| _version_ | 1818943213146210304 |
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| author | Chung-Ling Liang Po-Yuan Hsu Cheryl S. Ngo Wei Jie Seow Neerja Karnani Hong Pan Seang-Mei Saw Suh-Hang H. Juo |
| author_facet | Chung-Ling Liang Po-Yuan Hsu Cheryl S. Ngo Wei Jie Seow Neerja Karnani Hong Pan Seang-Mei Saw Suh-Hang H. Juo |
| author_sort | Chung-Ling Liang |
| collection | DOAJ |
| description | Abstract Purpose A recent meta-analysis revealed PAX6 as a risk gene for myopia. There is a link between PAX6 and HOXA9. Furthermore, HOXA9 has been reported to activate TGF-β that is a risk factor for myopia. We speculate HOXA9 may participate in myopia development. Methods The Singapore GUSTO birth cohort provides data on children’s cycloplegic refraction measured at age of 3 years and their methylation profile based on the umbilical cord DNA. The HOXA9 expression levels were measured in the eyes of mono-ocular form deprivation myopia in mice. The plasmid with the mouse HOXA9 cDNA was constructed and then transfected to mouse primary retinal pigment epithelial (RPE) cells. The expression levels of myopia-related genes and cell proliferation were measured in the HOXA9-overexpressed RPE cells. Results A total of 519 children had data on methylation profile and cycloplegic refraction. The mean spherical equivalent refraction (SE) was 0.90D. Among 8 SE outliers (worse than -2D), 7 children had HOXA9 hypomethylation. The HOXA9 levels in the retina of myopic eyes was 2.65-fold (p = 0.029; paired t-test) higher than the uncovered fellow eyes. When HOXA9 was over-expressed in the RPE cells, TGF-β, MMP2, FGF2 and IGF1R expression levels were dose-dependently increased by HOXA9. However, over-expression of HOXA9 had no significant influence on IGF1 or HGF expression. In addition, HOXA9 also increased RPE proliferation. Conclusion Based on the human, animal and cellular data, the transcription factor HOXA9 may promote the expression of pro-myopia genes and RPE proliferation, which eventually contribute to myopia development. |
| first_indexed | 2024-12-20T07:23:45Z |
| format | Article |
| id | doaj.art-c02715c1d5a14e4a8a2d9d0a2376d4cc |
| institution | Directory Open Access Journal |
| issn | 1471-2415 |
| language | English |
| last_indexed | 2024-12-20T07:23:45Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Ophthalmology |
| spelling | doaj.art-c02715c1d5a14e4a8a2d9d0a2376d4cc2022-12-21T19:48:37ZengBMCBMC Ophthalmology1471-24152019-01-011911810.1186/s12886-019-1038-9HOXA9 is a novel myopia risk geneChung-Ling Liang0Po-Yuan Hsu1Cheryl S. Ngo2Wei Jie Seow3Neerja Karnani4Hong Pan5Seang-Mei Saw6Suh-Hang H. Juo7Department of Ophthalmology, Asia University HospitalCenter for Myopia and Eye Disease, Department of Medical Research, China Medical University HospitalDepartment of Ophthalmology, National University HospitalSaw Swee Hock School of Public Health, National University of Singapore and National University Health SystemSingapore Institute for Clinical Sciences (SICS), A*STAR, Brenner Centre for Molecular MedicineSingapore Institute for Clinical Sciences (SICS), A*STAR, Brenner Centre for Molecular MedicineSaw Swee Hock School of Public Health, National University of Singapore and National University Health SystemCenter for Myopia and Eye Disease, Department of Medical Research, China Medical University HospitalAbstract Purpose A recent meta-analysis revealed PAX6 as a risk gene for myopia. There is a link between PAX6 and HOXA9. Furthermore, HOXA9 has been reported to activate TGF-β that is a risk factor for myopia. We speculate HOXA9 may participate in myopia development. Methods The Singapore GUSTO birth cohort provides data on children’s cycloplegic refraction measured at age of 3 years and their methylation profile based on the umbilical cord DNA. The HOXA9 expression levels were measured in the eyes of mono-ocular form deprivation myopia in mice. The plasmid with the mouse HOXA9 cDNA was constructed and then transfected to mouse primary retinal pigment epithelial (RPE) cells. The expression levels of myopia-related genes and cell proliferation were measured in the HOXA9-overexpressed RPE cells. Results A total of 519 children had data on methylation profile and cycloplegic refraction. The mean spherical equivalent refraction (SE) was 0.90D. Among 8 SE outliers (worse than -2D), 7 children had HOXA9 hypomethylation. The HOXA9 levels in the retina of myopic eyes was 2.65-fold (p = 0.029; paired t-test) higher than the uncovered fellow eyes. When HOXA9 was over-expressed in the RPE cells, TGF-β, MMP2, FGF2 and IGF1R expression levels were dose-dependently increased by HOXA9. However, over-expression of HOXA9 had no significant influence on IGF1 or HGF expression. In addition, HOXA9 also increased RPE proliferation. Conclusion Based on the human, animal and cellular data, the transcription factor HOXA9 may promote the expression of pro-myopia genes and RPE proliferation, which eventually contribute to myopia development.http://link.springer.com/article/10.1186/s12886-019-1038-9HOXA9PAX6microRNA-328Myopia |
| spellingShingle | Chung-Ling Liang Po-Yuan Hsu Cheryl S. Ngo Wei Jie Seow Neerja Karnani Hong Pan Seang-Mei Saw Suh-Hang H. Juo HOXA9 is a novel myopia risk gene BMC Ophthalmology HOXA9 PAX6 microRNA-328 Myopia |
| title | HOXA9 is a novel myopia risk gene |
| title_full | HOXA9 is a novel myopia risk gene |
| title_fullStr | HOXA9 is a novel myopia risk gene |
| title_full_unstemmed | HOXA9 is a novel myopia risk gene |
| title_short | HOXA9 is a novel myopia risk gene |
| title_sort | hoxa9 is a novel myopia risk gene |
| topic | HOXA9 PAX6 microRNA-328 Myopia |
| url | http://link.springer.com/article/10.1186/s12886-019-1038-9 |
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