Traumatic Optic Neuropathy Is Associated with Visual Impairment, Neurodegeneration, and Endoplasmic Reticulum Stress in Adolescent Mice
Traumatic brain injury (TBI) results in a number of impairments, often including visual symptoms. In some cases, visual impairments after head trauma are mediated by traumatic injury to the optic nerve, termed traumatic optic neuropathy (TON), which has few effective options for treatment. Using a m...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-04-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/10/5/996 |
| _version_ | 1797536498999885824 |
|---|---|
| author | Shelby M. Hetzer Fernanda Guilhaume-Correa Dylan Day Alicia Bedolla Nathan K. Evanson |
| author_facet | Shelby M. Hetzer Fernanda Guilhaume-Correa Dylan Day Alicia Bedolla Nathan K. Evanson |
| author_sort | Shelby M. Hetzer |
| collection | DOAJ |
| description | Traumatic brain injury (TBI) results in a number of impairments, often including visual symptoms. In some cases, visual impairments after head trauma are mediated by traumatic injury to the optic nerve, termed traumatic optic neuropathy (TON), which has few effective options for treatment. Using a murine closed-head weight-drop model of head trauma, we previously reported in adult mice that there is relatively selective injury to the optic tract and thalamic/brainstem projections of the visual system. In the current study, we performed blunt head trauma on adolescent C57BL/6 mice and investigated visual impairment in the primary visual system, now including the retina and using behavioral and histologic methods at new time points. After injury, mice displayed evidence of decreased optomotor responses illustrated by decreased optokinetic nystagmus. There did not appear to be a significant change in circadian locomotor behavior patterns, although there was an overall decrease in locomotor behavior in mice with head injury. There was evidence of axonal degeneration of optic nerve fibers with associated retinal ganglion cell death. There was also evidence of astrogliosis and microgliosis in major central targets of optic nerve projections. Further, there was elevated expression of endoplasmic reticulum (ER) stress markers in retinas of injured mice. Visual impairment, histologic markers of gliosis and neurodegeneration, and elevated ER stress marker expression persisted for at least 30 days after injury. The current results extend our previous findings in adult mice into adolescent mice, provide direct evidence of retinal ganglion cell injury after head trauma and suggest that axonal degeneration is associated with elevated ER stress in this model of TON. |
| first_indexed | 2024-03-10T12:01:33Z |
| format | Article |
| id | doaj.art-1942a6f1be2e4d8cb4af0ec954556652 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T12:01:33Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-1942a6f1be2e4d8cb4af0ec9545566522023-11-21T16:54:58ZengMDPI AGCells2073-44092021-04-0110599610.3390/cells10050996Traumatic Optic Neuropathy Is Associated with Visual Impairment, Neurodegeneration, and Endoplasmic Reticulum Stress in Adolescent MiceShelby M. Hetzer0Fernanda Guilhaume-Correa1Dylan Day2Alicia Bedolla3Nathan K. Evanson4Neuroscience Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USATranslational Biology, Medicine and Health, Virginia Polytechnic Institute and State University, Roanoke, VA 24016, USANeuroscience Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USANeuroscience Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USANeuroscience Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USATraumatic brain injury (TBI) results in a number of impairments, often including visual symptoms. In some cases, visual impairments after head trauma are mediated by traumatic injury to the optic nerve, termed traumatic optic neuropathy (TON), which has few effective options for treatment. Using a murine closed-head weight-drop model of head trauma, we previously reported in adult mice that there is relatively selective injury to the optic tract and thalamic/brainstem projections of the visual system. In the current study, we performed blunt head trauma on adolescent C57BL/6 mice and investigated visual impairment in the primary visual system, now including the retina and using behavioral and histologic methods at new time points. After injury, mice displayed evidence of decreased optomotor responses illustrated by decreased optokinetic nystagmus. There did not appear to be a significant change in circadian locomotor behavior patterns, although there was an overall decrease in locomotor behavior in mice with head injury. There was evidence of axonal degeneration of optic nerve fibers with associated retinal ganglion cell death. There was also evidence of astrogliosis and microgliosis in major central targets of optic nerve projections. Further, there was elevated expression of endoplasmic reticulum (ER) stress markers in retinas of injured mice. Visual impairment, histologic markers of gliosis and neurodegeneration, and elevated ER stress marker expression persisted for at least 30 days after injury. The current results extend our previous findings in adult mice into adolescent mice, provide direct evidence of retinal ganglion cell injury after head trauma and suggest that axonal degeneration is associated with elevated ER stress in this model of TON.https://www.mdpi.com/2073-4409/10/5/996traumatic optic neuropathyhead traumaadolescent head traumaER stressmice |
| spellingShingle | Shelby M. Hetzer Fernanda Guilhaume-Correa Dylan Day Alicia Bedolla Nathan K. Evanson Traumatic Optic Neuropathy Is Associated with Visual Impairment, Neurodegeneration, and Endoplasmic Reticulum Stress in Adolescent Mice Cells traumatic optic neuropathy head trauma adolescent head trauma ER stress mice |
| title | Traumatic Optic Neuropathy Is Associated with Visual Impairment, Neurodegeneration, and Endoplasmic Reticulum Stress in Adolescent Mice |
| title_full | Traumatic Optic Neuropathy Is Associated with Visual Impairment, Neurodegeneration, and Endoplasmic Reticulum Stress in Adolescent Mice |
| title_fullStr | Traumatic Optic Neuropathy Is Associated with Visual Impairment, Neurodegeneration, and Endoplasmic Reticulum Stress in Adolescent Mice |
| title_full_unstemmed | Traumatic Optic Neuropathy Is Associated with Visual Impairment, Neurodegeneration, and Endoplasmic Reticulum Stress in Adolescent Mice |
| title_short | Traumatic Optic Neuropathy Is Associated with Visual Impairment, Neurodegeneration, and Endoplasmic Reticulum Stress in Adolescent Mice |
| title_sort | traumatic optic neuropathy is associated with visual impairment neurodegeneration and endoplasmic reticulum stress in adolescent mice |
| topic | traumatic optic neuropathy head trauma adolescent head trauma ER stress mice |
| url | https://www.mdpi.com/2073-4409/10/5/996 |
| work_keys_str_mv | AT shelbymhetzer traumaticopticneuropathyisassociatedwithvisualimpairmentneurodegenerationandendoplasmicreticulumstressinadolescentmice AT fernandaguilhaumecorrea traumaticopticneuropathyisassociatedwithvisualimpairmentneurodegenerationandendoplasmicreticulumstressinadolescentmice AT dylanday traumaticopticneuropathyisassociatedwithvisualimpairmentneurodegenerationandendoplasmicreticulumstressinadolescentmice AT aliciabedolla traumaticopticneuropathyisassociatedwithvisualimpairmentneurodegenerationandendoplasmicreticulumstressinadolescentmice AT nathankevanson traumaticopticneuropathyisassociatedwithvisualimpairmentneurodegenerationandendoplasmicreticulumstressinadolescentmice |