Autophagy deficiency protects against ocular hypertension and glaucoma
Glaucoma encompasses a spectrum of disorders characterized by the chronic degeneration of retinal ganglion cell (RGC) axons and the progressive loss of RGCs, resulting in visual impairment. In this study, we investigated the effect of autophagy deficiency on two glaucoma hypertensive models, the DBA...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2024-12-01
|
| Series: | Autophagy Reports |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/27694127.2023.2285214 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846136332562202624 |
|---|---|
| author | Angela Dixon Myoung Sup Shim April Nettesheim Aislyn Coyne Chien-Chia Su Haiyan Gong Paloma B. Liton |
| author_facet | Angela Dixon Myoung Sup Shim April Nettesheim Aislyn Coyne Chien-Chia Su Haiyan Gong Paloma B. Liton |
| author_sort | Angela Dixon |
| collection | DOAJ |
| description | Glaucoma encompasses a spectrum of disorders characterized by the chronic degeneration of retinal ganglion cell (RGC) axons and the progressive loss of RGCs, resulting in visual impairment. In this study, we investigated the effect of autophagy deficiency on two glaucoma hypertensive models, the DBA/2J spontaneous glaucoma model, and the TGFβ2 (transforming growth factor β2) chronic ocular hypertensive model. For this, we used the Atg4b−/− and DBA/2J-Atg4b−/− mice, this latter generated in our laboratory via CRISPR/Cas9 technology, which display impaired autophagy. In contrast to littermate WT controls, mice deficient in Atg4B, did not develop glaucomatous elevation of intraocular pressure (IOP). Moreover, autophagy deficiency protected against RGC death and optic nerve atrophy. Collectively, our data supports a pathogenic role of autophagy in the context of ocular hypertension and glaucoma.Abbreviations: ATG4B: Autophagy-related 4B; BAX: BCL2-associated X protein; BECN1: Beclin 1; BID: BH3 interacting domain death agonist; CASP8: Caspase 8; IOP: Intraocular Pressure; MAP1LC3B: microtubule-associated proteins 1B; ON: Optic Nerve; RGC: Retinal Ganglion Cells; SQSTSM1: Sequestosome 1; TBK1: TANK-binding kinase 1; TGFβ2: Transforming Growth Factor β2; WT: Wild Type. |
| format | Article |
| id | doaj-art-868fae2bf19d49f1a28a82eb56a4edb1 |
| institution | Kabale University |
| issn | 2769-4127 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autophagy Reports |
| spelling | doaj-art-868fae2bf19d49f1a28a82eb56a4edb12024-12-09T07:19:32ZengTaylor & Francis GroupAutophagy Reports2769-41272024-12-013110.1080/27694127.2023.2285214Autophagy deficiency protects against ocular hypertension and glaucomaAngela Dixon0Myoung Sup Shim1April Nettesheim2Aislyn Coyne3Chien-Chia Su4Haiyan Gong5Paloma B. Liton6Department of Ophthalmology & Pathology, Duke University, Durham, NC, 27705, USADepartment of Ophthalmology & Pathology, Duke University, Durham, NC, 27705, USADepartment of Ophthalmology & Pathology, Duke University, Durham, NC, 27705, USADepartment of Ophthalmology & Pathology, Duke University, Durham, NC, 27705, USADepartment of Ophthalmology & Pathology, Duke University, Durham, NC, 27705, USADepartment of Ophthalmology, Boston University School of Medicine, Boston, MA, 02118, USADepartment of Ophthalmology & Pathology, Duke University, Durham, NC, 27705, USAGlaucoma encompasses a spectrum of disorders characterized by the chronic degeneration of retinal ganglion cell (RGC) axons and the progressive loss of RGCs, resulting in visual impairment. In this study, we investigated the effect of autophagy deficiency on two glaucoma hypertensive models, the DBA/2J spontaneous glaucoma model, and the TGFβ2 (transforming growth factor β2) chronic ocular hypertensive model. For this, we used the Atg4b−/− and DBA/2J-Atg4b−/− mice, this latter generated in our laboratory via CRISPR/Cas9 technology, which display impaired autophagy. In contrast to littermate WT controls, mice deficient in Atg4B, did not develop glaucomatous elevation of intraocular pressure (IOP). Moreover, autophagy deficiency protected against RGC death and optic nerve atrophy. Collectively, our data supports a pathogenic role of autophagy in the context of ocular hypertension and glaucoma.Abbreviations: ATG4B: Autophagy-related 4B; BAX: BCL2-associated X protein; BECN1: Beclin 1; BID: BH3 interacting domain death agonist; CASP8: Caspase 8; IOP: Intraocular Pressure; MAP1LC3B: microtubule-associated proteins 1B; ON: Optic Nerve; RGC: Retinal Ganglion Cells; SQSTSM1: Sequestosome 1; TBK1: TANK-binding kinase 1; TGFβ2: Transforming Growth Factor β2; WT: Wild Type.https://www.tandfonline.com/doi/10.1080/27694127.2023.2285214Autophagyocular hypertensionglaucomaRGCoptic nerveDBA/2J |
| spellingShingle | Angela Dixon Myoung Sup Shim April Nettesheim Aislyn Coyne Chien-Chia Su Haiyan Gong Paloma B. Liton Autophagy deficiency protects against ocular hypertension and glaucoma Autophagy Reports Autophagy ocular hypertension glaucoma RGC optic nerve DBA/2J |
| title | Autophagy deficiency protects against ocular hypertension and glaucoma |
| title_full | Autophagy deficiency protects against ocular hypertension and glaucoma |
| title_fullStr | Autophagy deficiency protects against ocular hypertension and glaucoma |
| title_full_unstemmed | Autophagy deficiency protects against ocular hypertension and glaucoma |
| title_short | Autophagy deficiency protects against ocular hypertension and glaucoma |
| title_sort | autophagy deficiency protects against ocular hypertension and glaucoma |
| topic | Autophagy ocular hypertension glaucoma RGC optic nerve DBA/2J |
| url | https://www.tandfonline.com/doi/10.1080/27694127.2023.2285214 |
| work_keys_str_mv | AT angeladixon autophagydeficiencyprotectsagainstocularhypertensionandglaucoma AT myoungsupshim autophagydeficiencyprotectsagainstocularhypertensionandglaucoma AT aprilnettesheim autophagydeficiencyprotectsagainstocularhypertensionandglaucoma AT aislyncoyne autophagydeficiencyprotectsagainstocularhypertensionandglaucoma AT chienchiasu autophagydeficiencyprotectsagainstocularhypertensionandglaucoma AT haiyangong autophagydeficiencyprotectsagainstocularhypertensionandglaucoma AT palomabliton autophagydeficiencyprotectsagainstocularhypertensionandglaucoma |