Glaucoma Heritability: Molecular Mechanisms of Disease
Glaucoma is one of the world’s leading causes of irreversible blindness. A complex, multifactorial disease, the underlying pathogenesis and reasons for disease progression are not fully understood. The most common form of glaucoma, primary open-angle glaucoma (POAG), was traditionally understood to...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-07-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/8/1135 |
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| author | Ryan Zukerman Alon Harris Francesco Oddone Brent Siesky Alice Verticchio Vercellin Thomas A. Ciulla |
| author_facet | Ryan Zukerman Alon Harris Francesco Oddone Brent Siesky Alice Verticchio Vercellin Thomas A. Ciulla |
| author_sort | Ryan Zukerman |
| collection | DOAJ |
| description | Glaucoma is one of the world’s leading causes of irreversible blindness. A complex, multifactorial disease, the underlying pathogenesis and reasons for disease progression are not fully understood. The most common form of glaucoma, primary open-angle glaucoma (POAG), was traditionally understood to be the result of elevated intraocular pressure (IOP), leading to optic nerve damage and functional vision loss. Recently, researchers have suggested that POAG may have an underlying genetic component. In fact, studies of genetic association and heritability have yielded encouraging results showing that glaucoma may be influenced by genetic factors, and estimates for the heritability of POAG and disease-related endophenotypes show encouraging results. However, the vast majority of the underlying genetic variants and their molecular mechanisms have not been elucidated. Several genes have been suggested to have molecular mechanisms contributing to alterations in key endophenotypes such as IOP (<i>LMX1B</i>, <i>MADD</i>, <i>NR1H3</i>, and <i>SEPT9)</i>, and VCDR (<i>ABCA1</i>, <i>ELN</i>, <i>ASAP1</i>, and <i>ATOH7</i>). Still, genetic studies about glaucoma and its molecular mechanisms are limited by the multifactorial nature of the disease and the large number of genes that have been identified to have an association with glaucoma. Therefore, further study into the molecular mechanisms of the disease itself are required for the future development of therapies targeted at genes leading to POAG endophenotypes and, therefore, increased risk of disease. |
| first_indexed | 2024-03-10T08:47:56Z |
| format | Article |
| id | doaj.art-95ec30ebafcb43a88503e8c99154a246 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T08:47:56Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-95ec30ebafcb43a88503e8c99154a2462023-11-22T07:45:02ZengMDPI AGGenes2073-44252021-07-01128113510.3390/genes12081135Glaucoma Heritability: Molecular Mechanisms of DiseaseRyan Zukerman0Alon Harris1Francesco Oddone2Brent Siesky3Alice Verticchio Vercellin4Thomas A. Ciulla5Department of Ophthalmology, Icahn School of Medicine at Mt. Sinai, New York, NY 10029, USADepartment of Ophthalmology, Icahn School of Medicine at Mt. Sinai, New York, NY 10029, USAIRCCS–Fondazione Bietti, 00198 Rome, ItalyDepartment of Ophthalmology, Icahn School of Medicine at Mt. Sinai, New York, NY 10029, USADepartment of Ophthalmology, Icahn School of Medicine at Mt. Sinai, New York, NY 10029, USAMidwest Eye Institute, Indianapolis, IN 46290, USAGlaucoma is one of the world’s leading causes of irreversible blindness. A complex, multifactorial disease, the underlying pathogenesis and reasons for disease progression are not fully understood. The most common form of glaucoma, primary open-angle glaucoma (POAG), was traditionally understood to be the result of elevated intraocular pressure (IOP), leading to optic nerve damage and functional vision loss. Recently, researchers have suggested that POAG may have an underlying genetic component. In fact, studies of genetic association and heritability have yielded encouraging results showing that glaucoma may be influenced by genetic factors, and estimates for the heritability of POAG and disease-related endophenotypes show encouraging results. However, the vast majority of the underlying genetic variants and their molecular mechanisms have not been elucidated. Several genes have been suggested to have molecular mechanisms contributing to alterations in key endophenotypes such as IOP (<i>LMX1B</i>, <i>MADD</i>, <i>NR1H3</i>, and <i>SEPT9)</i>, and VCDR (<i>ABCA1</i>, <i>ELN</i>, <i>ASAP1</i>, and <i>ATOH7</i>). Still, genetic studies about glaucoma and its molecular mechanisms are limited by the multifactorial nature of the disease and the large number of genes that have been identified to have an association with glaucoma. Therefore, further study into the molecular mechanisms of the disease itself are required for the future development of therapies targeted at genes leading to POAG endophenotypes and, therefore, increased risk of disease.https://www.mdpi.com/2073-4425/12/8/1135glaucomageneticsheritabilityprimary open-angle glaucomaintraocular pressurecup-to-disc ratio |
| spellingShingle | Ryan Zukerman Alon Harris Francesco Oddone Brent Siesky Alice Verticchio Vercellin Thomas A. Ciulla Glaucoma Heritability: Molecular Mechanisms of Disease Genes glaucoma genetics heritability primary open-angle glaucoma intraocular pressure cup-to-disc ratio |
| title | Glaucoma Heritability: Molecular Mechanisms of Disease |
| title_full | Glaucoma Heritability: Molecular Mechanisms of Disease |
| title_fullStr | Glaucoma Heritability: Molecular Mechanisms of Disease |
| title_full_unstemmed | Glaucoma Heritability: Molecular Mechanisms of Disease |
| title_short | Glaucoma Heritability: Molecular Mechanisms of Disease |
| title_sort | glaucoma heritability molecular mechanisms of disease |
| topic | glaucoma genetics heritability primary open-angle glaucoma intraocular pressure cup-to-disc ratio |
| url | https://www.mdpi.com/2073-4425/12/8/1135 |
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