Insight from <i>OPN1LW</i> Gene Haplotypes into the Cause and Prevention of Myopia
Nearsightedness (myopia) is a global health problem of staggering proportions that has driven the hunt for environmental and genetic risk factors in hopes of gaining insight into the underlying mechanism and providing new avenues of intervention. Myopia is the dominant risk factor for leading causes...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-05-01
|
| Series: | Genes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4425/13/6/942 |
| _version_ | 1797487149326532608 |
|---|---|
| author | Maureen Neitz Melissa Wagner-Schuman Jessica S. Rowlan James A. Kuchenbecker Jay Neitz |
| author_facet | Maureen Neitz Melissa Wagner-Schuman Jessica S. Rowlan James A. Kuchenbecker Jay Neitz |
| author_sort | Maureen Neitz |
| collection | DOAJ |
| description | Nearsightedness (myopia) is a global health problem of staggering proportions that has driven the hunt for environmental and genetic risk factors in hopes of gaining insight into the underlying mechanism and providing new avenues of intervention. Myopia is the dominant risk factor for leading causes of blindness, including myopic maculopathy and retinal detachment. The fundamental defect in myopia—an excessively elongated eyeball—causes blurry distance vision that is correctable with lenses or surgery, but the risk of blindness remains. Haplotypes of the long-wavelength and middle-wavelength cone opsin genes (<i>OPN1LW</i> and <i>OPN1MW</i>, respectively) that exhibit profound exon-3 skipping during pre-messenger RNA splicing are associated with high myopia. Cone photoreceptors expressing these haplotypes are nearly devoid of photopigment. Conversely, cones in the same retina that express non-skipping haplotypes are relatively full of photopigment. We hypothesized that abnormal contrast signals arising from adjacent cones differing in photopigment content stimulate axial elongation, and spectacles that reduce contrast may significantly slow myopia progression. We tested for an association between spherical equivalent refraction and <i>OPN1LW</i> haplotype in males of European ancestry as determined by long-distance PCR and Sanger sequencing and identified <i>OPN1LW</i> exon 3 haplotypes that increase the risk of common myopia. We also evaluated the effects of contrast-reducing spectacles lenses on myopia progression in children. The work presented here provides new insight into the cause and prevention of myopia progression. |
| first_indexed | 2024-03-09T23:43:27Z |
| format | Article |
| id | doaj.art-086bd842a4a54e2888ac5b597c247b43 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T23:43:27Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-086bd842a4a54e2888ac5b597c247b432023-11-23T16:46:39ZengMDPI AGGenes2073-44252022-05-0113694210.3390/genes13060942Insight from <i>OPN1LW</i> Gene Haplotypes into the Cause and Prevention of MyopiaMaureen Neitz0Melissa Wagner-Schuman1Jessica S. Rowlan2James A. Kuchenbecker3Jay Neitz4Department of Ophthalmology, University of Washington, Seattle, WA 98109, USADepartment of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USADepartment of Ophthalmology, University of Washington, Seattle, WA 98109, USADepartment of Ophthalmology, University of Washington, Seattle, WA 98109, USADepartment of Ophthalmology, University of Washington, Seattle, WA 98109, USANearsightedness (myopia) is a global health problem of staggering proportions that has driven the hunt for environmental and genetic risk factors in hopes of gaining insight into the underlying mechanism and providing new avenues of intervention. Myopia is the dominant risk factor for leading causes of blindness, including myopic maculopathy and retinal detachment. The fundamental defect in myopia—an excessively elongated eyeball—causes blurry distance vision that is correctable with lenses or surgery, but the risk of blindness remains. Haplotypes of the long-wavelength and middle-wavelength cone opsin genes (<i>OPN1LW</i> and <i>OPN1MW</i>, respectively) that exhibit profound exon-3 skipping during pre-messenger RNA splicing are associated with high myopia. Cone photoreceptors expressing these haplotypes are nearly devoid of photopigment. Conversely, cones in the same retina that express non-skipping haplotypes are relatively full of photopigment. We hypothesized that abnormal contrast signals arising from adjacent cones differing in photopigment content stimulate axial elongation, and spectacles that reduce contrast may significantly slow myopia progression. We tested for an association between spherical equivalent refraction and <i>OPN1LW</i> haplotype in males of European ancestry as determined by long-distance PCR and Sanger sequencing and identified <i>OPN1LW</i> exon 3 haplotypes that increase the risk of common myopia. We also evaluated the effects of contrast-reducing spectacles lenses on myopia progression in children. The work presented here provides new insight into the cause and prevention of myopia progression.https://www.mdpi.com/2073-4425/13/6/942myopia geneticscone opsin genesXq28exon skippingsplicing mutation |
| spellingShingle | Maureen Neitz Melissa Wagner-Schuman Jessica S. Rowlan James A. Kuchenbecker Jay Neitz Insight from <i>OPN1LW</i> Gene Haplotypes into the Cause and Prevention of Myopia Genes myopia genetics cone opsin genes Xq28 exon skipping splicing mutation |
| title | Insight from <i>OPN1LW</i> Gene Haplotypes into the Cause and Prevention of Myopia |
| title_full | Insight from <i>OPN1LW</i> Gene Haplotypes into the Cause and Prevention of Myopia |
| title_fullStr | Insight from <i>OPN1LW</i> Gene Haplotypes into the Cause and Prevention of Myopia |
| title_full_unstemmed | Insight from <i>OPN1LW</i> Gene Haplotypes into the Cause and Prevention of Myopia |
| title_short | Insight from <i>OPN1LW</i> Gene Haplotypes into the Cause and Prevention of Myopia |
| title_sort | insight from i opn1lw i gene haplotypes into the cause and prevention of myopia |
| topic | myopia genetics cone opsin genes Xq28 exon skipping splicing mutation |
| url | https://www.mdpi.com/2073-4425/13/6/942 |
| work_keys_str_mv | AT maureenneitz insightfromiopn1lwigenehaplotypesintothecauseandpreventionofmyopia AT melissawagnerschuman insightfromiopn1lwigenehaplotypesintothecauseandpreventionofmyopia AT jessicasrowlan insightfromiopn1lwigenehaplotypesintothecauseandpreventionofmyopia AT jamesakuchenbecker insightfromiopn1lwigenehaplotypesintothecauseandpreventionofmyopia AT jayneitz insightfromiopn1lwigenehaplotypesintothecauseandpreventionofmyopia |