Clinical Role of Epigenetics and Network Analysis in Eye Diseases: A Translational Science Review
Network medicine is a molecular-bioinformatic approach analyzing gene-gene interactions that can perturb the human interactome. This review focuses on epigenetic changes involved in several ocular diseases, such as DNA methylation, histone and nonhistone post-translational modifications, and noncodi...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of Ophthalmology |
| Online Access: | http://dx.doi.org/10.1155/2019/2424956 |
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| _version_ | 1832548956876308480 |
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| author | Michele Lanza Giuditta Benincasa Dario Costa Claudio Napoli |
| author_facet | Michele Lanza Giuditta Benincasa Dario Costa Claudio Napoli |
| author_sort | Michele Lanza |
| collection | DOAJ |
| description | Network medicine is a molecular-bioinformatic approach analyzing gene-gene interactions that can perturb the human interactome. This review focuses on epigenetic changes involved in several ocular diseases, such as DNA methylation, histone and nonhistone post-translational modifications, and noncoding RNA regulators. Although changes in aberrant DNA methylation play a major role in the pathogenesis of most ocular diseases, histone modifications are seldom investigated. Hypermethylation in TGM-2 and hypomethylation in MMP-2/CD24 promoter genes may play a crucial role in pterygium development; hypermethylation in regulatory regions of GSTP1 and OGG1 genes appear to be diagnostic biomarkers of cataract; hypomethylation of TGF-β1 promoter may trigger glaucoma onset; hypermethylation of the LOXL1 gene might be associated with pseudoexfoliation syndrome. A large panel of upregulated micro-RNAs (miRNAs), including hsa-hsa-miR-494, hsa-let-7e, hsa-miR-513-1, hsa-miR-513-2, hsa-miR-518c, hsa-miR-129-1, hsa-miR-129-2, hsa-miR-198, hsa-miR-492, hsa-miR-498, hsa-miR-320, hsa-miR-503, and hsa-miR-373,∗ may have a putative role in the development of retinoblastoma. Hypermethylation of H3K4 and hypomethylation of H3K27 at the TGFBIp locus are putative pathogenic mechanisms involved in corneal dystrophies. Determining how, where, and when specific epigenetic changes trigger ocular diseases may provide useful clinical biomarkers for their prevention, diagnosis, and management, as well as innovative drug targets. PF-04523655, a 19-nucleotide methylated double-stranded siRNA targeting the RTP80 gene, showed a dose-related improvement in best-corrected visual acuity (BCVA) in patients affected by diabetic macular edema. The observed results support a clinical network-based research program aimed to clarify the role of epigenetic regulators in the development of ocular diseases and personalized therapy. |
| format | Article |
| id | doaj-art-78be31527ca743c1b5a09595cc399525 |
| institution | Kabale University |
| issn | 2090-004X 2090-0058 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Ophthalmology |
| spelling | doaj-art-78be31527ca743c1b5a09595cc3995252025-02-03T06:12:34ZengWileyJournal of Ophthalmology2090-004X2090-00582019-01-01201910.1155/2019/24249562424956Clinical Role of Epigenetics and Network Analysis in Eye Diseases: A Translational Science ReviewMichele Lanza0Giuditta Benincasa1Dario Costa2Claudio Napoli3Multidisciplinary Department of Medical, Surgical and Dental Sciences, Campania University Luigi Vanvitelli, Naples, ItalyClinical Department of Internal Medicine and Specialistics, Department of Advanced Clinical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyU.O.C. Division of Immunohematology, Transfusion Medicine and Transplant Immunology, Department of Internal Medicine and Specialistics, University of Campania “Luigi Vanvitelli”, Naples, ItalyClinical Department of Internal Medicine and Specialistics, Department of Advanced Clinical and Surgical Sciences, University of Campania “Luigi Vanvitelli”, 80138 Naples, ItalyNetwork medicine is a molecular-bioinformatic approach analyzing gene-gene interactions that can perturb the human interactome. This review focuses on epigenetic changes involved in several ocular diseases, such as DNA methylation, histone and nonhistone post-translational modifications, and noncoding RNA regulators. Although changes in aberrant DNA methylation play a major role in the pathogenesis of most ocular diseases, histone modifications are seldom investigated. Hypermethylation in TGM-2 and hypomethylation in MMP-2/CD24 promoter genes may play a crucial role in pterygium development; hypermethylation in regulatory regions of GSTP1 and OGG1 genes appear to be diagnostic biomarkers of cataract; hypomethylation of TGF-β1 promoter may trigger glaucoma onset; hypermethylation of the LOXL1 gene might be associated with pseudoexfoliation syndrome. A large panel of upregulated micro-RNAs (miRNAs), including hsa-hsa-miR-494, hsa-let-7e, hsa-miR-513-1, hsa-miR-513-2, hsa-miR-518c, hsa-miR-129-1, hsa-miR-129-2, hsa-miR-198, hsa-miR-492, hsa-miR-498, hsa-miR-320, hsa-miR-503, and hsa-miR-373,∗ may have a putative role in the development of retinoblastoma. Hypermethylation of H3K4 and hypomethylation of H3K27 at the TGFBIp locus are putative pathogenic mechanisms involved in corneal dystrophies. Determining how, where, and when specific epigenetic changes trigger ocular diseases may provide useful clinical biomarkers for their prevention, diagnosis, and management, as well as innovative drug targets. PF-04523655, a 19-nucleotide methylated double-stranded siRNA targeting the RTP80 gene, showed a dose-related improvement in best-corrected visual acuity (BCVA) in patients affected by diabetic macular edema. The observed results support a clinical network-based research program aimed to clarify the role of epigenetic regulators in the development of ocular diseases and personalized therapy.http://dx.doi.org/10.1155/2019/2424956 |
| spellingShingle | Michele Lanza Giuditta Benincasa Dario Costa Claudio Napoli Clinical Role of Epigenetics and Network Analysis in Eye Diseases: A Translational Science Review Journal of Ophthalmology |
| title | Clinical Role of Epigenetics and Network Analysis in Eye Diseases: A Translational Science Review |
| title_full | Clinical Role of Epigenetics and Network Analysis in Eye Diseases: A Translational Science Review |
| title_fullStr | Clinical Role of Epigenetics and Network Analysis in Eye Diseases: A Translational Science Review |
| title_full_unstemmed | Clinical Role of Epigenetics and Network Analysis in Eye Diseases: A Translational Science Review |
| title_short | Clinical Role of Epigenetics and Network Analysis in Eye Diseases: A Translational Science Review |
| title_sort | clinical role of epigenetics and network analysis in eye diseases a translational science review |
| url | http://dx.doi.org/10.1155/2019/2424956 |
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