Regional Gene Expression in the Retina, Optic Nerve Head, and Optic Nerve of Mice with Optic Nerve Crush and Experimental Glaucoma
A major risk factor for glaucomatous optic neuropathy is the level of intraocular pressure (IOP), which can lead to retinal ganglion cell axon injury and cell death. The optic nerve has a rostral unmyelinated portion at the optic nerve head followed by a caudal myelinated region. The unmyelinated re...
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MDPI AG
2023-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/18/13719 |
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| author | Casey J. Keuthan Julie A. Schaub Meihan Wei Weixiang Fang Sarah Quillen Elizabeth Kimball Thomas V. Johnson Hongkai Ji Donald J. Zack Harry A. Quigley |
| author_facet | Casey J. Keuthan Julie A. Schaub Meihan Wei Weixiang Fang Sarah Quillen Elizabeth Kimball Thomas V. Johnson Hongkai Ji Donald J. Zack Harry A. Quigley |
| author_sort | Casey J. Keuthan |
| collection | DOAJ |
| description | A major risk factor for glaucomatous optic neuropathy is the level of intraocular pressure (IOP), which can lead to retinal ganglion cell axon injury and cell death. The optic nerve has a rostral unmyelinated portion at the optic nerve head followed by a caudal myelinated region. The unmyelinated region is differentially susceptible to IOP-induced damage in rodent models and human glaucoma. While several studies have analyzed gene expression changes in the mouse optic nerve following optic nerve injury, few were designed to consider the regional gene expression differences that exist between these distinct areas. We performed bulk RNA-sequencing on the retina and separately micro-dissected unmyelinated and myelinated optic nerve regions from naïve C57BL/6 mice, mice after optic nerve crush, and mice with microbead-induced experimental glaucoma (total = 36). Gene expression patterns in the naïve unmyelinated optic nerve showed significant enrichment of the Wnt, Hippo, PI3K-Akt, and transforming growth factor β pathways, as well as extracellular matrix–receptor and cell membrane signaling pathways, compared to the myelinated optic nerve and retina. Gene expression changes induced by both injuries were more extensive in the myelinated optic nerve than the unmyelinated region, and greater after nerve crush than glaucoma. Changes present three and fourteen days after injury largely subsided by six weeks. Gene markers of reactive astrocytes did not consistently differ between injury states. Overall, the transcriptomic phenotype of the mouse unmyelinated optic nerve was significantly different from immediately adjacent tissues, likely dominated by expression in astrocytes, whose junctional complexes are inherently important in responding to IOP elevation. |
| first_indexed | 2024-03-10T22:41:47Z |
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| id | doaj.art-f8034c9f02e64b5eb5b27706db54c72a |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T22:41:47Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f8034c9f02e64b5eb5b27706db54c72a2023-11-19T11:02:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124181371910.3390/ijms241813719Regional Gene Expression in the Retina, Optic Nerve Head, and Optic Nerve of Mice with Optic Nerve Crush and Experimental GlaucomaCasey J. Keuthan0Julie A. Schaub1Meihan Wei2Weixiang Fang3Sarah Quillen4Elizabeth Kimball5Thomas V. Johnson6Hongkai Ji7Donald J. Zack8Harry A. Quigley9Department of Ophthalmology, Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USADepartment of Ophthalmology, Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USADepartment of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USADepartment of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USADepartment of Ophthalmology, Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USADepartment of Ophthalmology, Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USADepartment of Ophthalmology, Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USADepartment of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USADepartment of Ophthalmology, Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USADepartment of Ophthalmology, Wilmer Eye Institute, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USAA major risk factor for glaucomatous optic neuropathy is the level of intraocular pressure (IOP), which can lead to retinal ganglion cell axon injury and cell death. The optic nerve has a rostral unmyelinated portion at the optic nerve head followed by a caudal myelinated region. The unmyelinated region is differentially susceptible to IOP-induced damage in rodent models and human glaucoma. While several studies have analyzed gene expression changes in the mouse optic nerve following optic nerve injury, few were designed to consider the regional gene expression differences that exist between these distinct areas. We performed bulk RNA-sequencing on the retina and separately micro-dissected unmyelinated and myelinated optic nerve regions from naïve C57BL/6 mice, mice after optic nerve crush, and mice with microbead-induced experimental glaucoma (total = 36). Gene expression patterns in the naïve unmyelinated optic nerve showed significant enrichment of the Wnt, Hippo, PI3K-Akt, and transforming growth factor β pathways, as well as extracellular matrix–receptor and cell membrane signaling pathways, compared to the myelinated optic nerve and retina. Gene expression changes induced by both injuries were more extensive in the myelinated optic nerve than the unmyelinated region, and greater after nerve crush than glaucoma. Changes present three and fourteen days after injury largely subsided by six weeks. Gene markers of reactive astrocytes did not consistently differ between injury states. Overall, the transcriptomic phenotype of the mouse unmyelinated optic nerve was significantly different from immediately adjacent tissues, likely dominated by expression in astrocytes, whose junctional complexes are inherently important in responding to IOP elevation.https://www.mdpi.com/1422-0067/24/18/13719gene expressiontranscriptomicsoptic nerveretinaastrocytesglaucoma |
| spellingShingle | Casey J. Keuthan Julie A. Schaub Meihan Wei Weixiang Fang Sarah Quillen Elizabeth Kimball Thomas V. Johnson Hongkai Ji Donald J. Zack Harry A. Quigley Regional Gene Expression in the Retina, Optic Nerve Head, and Optic Nerve of Mice with Optic Nerve Crush and Experimental Glaucoma International Journal of Molecular Sciences gene expression transcriptomics optic nerve retina astrocytes glaucoma |
| title | Regional Gene Expression in the Retina, Optic Nerve Head, and Optic Nerve of Mice with Optic Nerve Crush and Experimental Glaucoma |
| title_full | Regional Gene Expression in the Retina, Optic Nerve Head, and Optic Nerve of Mice with Optic Nerve Crush and Experimental Glaucoma |
| title_fullStr | Regional Gene Expression in the Retina, Optic Nerve Head, and Optic Nerve of Mice with Optic Nerve Crush and Experimental Glaucoma |
| title_full_unstemmed | Regional Gene Expression in the Retina, Optic Nerve Head, and Optic Nerve of Mice with Optic Nerve Crush and Experimental Glaucoma |
| title_short | Regional Gene Expression in the Retina, Optic Nerve Head, and Optic Nerve of Mice with Optic Nerve Crush and Experimental Glaucoma |
| title_sort | regional gene expression in the retina optic nerve head and optic nerve of mice with optic nerve crush and experimental glaucoma |
| topic | gene expression transcriptomics optic nerve retina astrocytes glaucoma |
| url | https://www.mdpi.com/1422-0067/24/18/13719 |
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