Non-image-forming light driven functions are preserved in a mouse model of autosomal dominant optic atrophy.
Autosomal dominant optic atrophy (ADOA) is a slowly progressive optic neuropathy that has been associated with mutations of the OPA1 gene. In patients, the disease primarily affects the retinal ganglion cells (RGCs) and causes optic nerve atrophy and visual loss. A subset of RGCs are intrinsically p...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3569441?pdf=render |
| _version_ | 1819066152060452864 |
|---|---|
| author | Georgia Perganta Alun R Barnard Christiana Katti Athanasios Vachtsevanos Ron H Douglas Robert E MacLaren Marcela Votruba Sumathi Sekaran |
| author_facet | Georgia Perganta Alun R Barnard Christiana Katti Athanasios Vachtsevanos Ron H Douglas Robert E MacLaren Marcela Votruba Sumathi Sekaran |
| author_sort | Georgia Perganta |
| collection | DOAJ |
| description | Autosomal dominant optic atrophy (ADOA) is a slowly progressive optic neuropathy that has been associated with mutations of the OPA1 gene. In patients, the disease primarily affects the retinal ganglion cells (RGCs) and causes optic nerve atrophy and visual loss. A subset of RGCs are intrinsically photosensitive, express the photopigment melanopsin and drive non-image-forming (NIF) visual functions including light driven circadian and sleep behaviours and the pupil light reflex. Given the RGC pathology in ADOA, disruption of NIF functions might be predicted. Interestingly in ADOA patients the pupil light reflex was preserved, although NIF behavioural outputs were not examined. The B6; C3-Opa1(Q285STOP) mouse model of ADOA displays optic nerve abnormalities, RGC dendropathy and functional visual disruption. We performed a comprehensive assessment of light driven NIF functions in this mouse model using wheel running activity monitoring, videotracking and pupillometry. Opa1 mutant mice entrained their activity rhythm to the external light/dark cycle, suppressed their activity in response to acute light exposure at night, generated circadian phase shift responses to 480 nm and 525 nm pulses, demonstrated immobility-defined sleep induction following exposure to a brief light pulse at night and exhibited an intensity dependent pupil light reflex. There were no significant differences in any parameter tested relative to wildtype littermate controls. Furthermore, there was no significant difference in the number of melanopsin-expressing RGCs, cell morphology or melanopsin transcript levels between genotypes. Taken together, these findings suggest the preservation of NIF functions in Opa1 mutants. The results provide support to growing evidence that the melanopsin-expressing RGCs are protected in mitochondrial optic neuropathies. |
| first_indexed | 2024-12-21T15:57:49Z |
| format | Article |
| id | doaj.art-14f80289780343f1b4994e58db16d710 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T15:57:49Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-14f80289780343f1b4994e58db16d7102022-12-21T18:58:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5635010.1371/journal.pone.0056350Non-image-forming light driven functions are preserved in a mouse model of autosomal dominant optic atrophy.Georgia PergantaAlun R BarnardChristiana KattiAthanasios VachtsevanosRon H DouglasRobert E MacLarenMarcela VotrubaSumathi SekaranAutosomal dominant optic atrophy (ADOA) is a slowly progressive optic neuropathy that has been associated with mutations of the OPA1 gene. In patients, the disease primarily affects the retinal ganglion cells (RGCs) and causes optic nerve atrophy and visual loss. A subset of RGCs are intrinsically photosensitive, express the photopigment melanopsin and drive non-image-forming (NIF) visual functions including light driven circadian and sleep behaviours and the pupil light reflex. Given the RGC pathology in ADOA, disruption of NIF functions might be predicted. Interestingly in ADOA patients the pupil light reflex was preserved, although NIF behavioural outputs were not examined. The B6; C3-Opa1(Q285STOP) mouse model of ADOA displays optic nerve abnormalities, RGC dendropathy and functional visual disruption. We performed a comprehensive assessment of light driven NIF functions in this mouse model using wheel running activity monitoring, videotracking and pupillometry. Opa1 mutant mice entrained their activity rhythm to the external light/dark cycle, suppressed their activity in response to acute light exposure at night, generated circadian phase shift responses to 480 nm and 525 nm pulses, demonstrated immobility-defined sleep induction following exposure to a brief light pulse at night and exhibited an intensity dependent pupil light reflex. There were no significant differences in any parameter tested relative to wildtype littermate controls. Furthermore, there was no significant difference in the number of melanopsin-expressing RGCs, cell morphology or melanopsin transcript levels between genotypes. Taken together, these findings suggest the preservation of NIF functions in Opa1 mutants. The results provide support to growing evidence that the melanopsin-expressing RGCs are protected in mitochondrial optic neuropathies.http://europepmc.org/articles/PMC3569441?pdf=render |
| spellingShingle | Georgia Perganta Alun R Barnard Christiana Katti Athanasios Vachtsevanos Ron H Douglas Robert E MacLaren Marcela Votruba Sumathi Sekaran Non-image-forming light driven functions are preserved in a mouse model of autosomal dominant optic atrophy. PLoS ONE |
| title | Non-image-forming light driven functions are preserved in a mouse model of autosomal dominant optic atrophy. |
| title_full | Non-image-forming light driven functions are preserved in a mouse model of autosomal dominant optic atrophy. |
| title_fullStr | Non-image-forming light driven functions are preserved in a mouse model of autosomal dominant optic atrophy. |
| title_full_unstemmed | Non-image-forming light driven functions are preserved in a mouse model of autosomal dominant optic atrophy. |
| title_short | Non-image-forming light driven functions are preserved in a mouse model of autosomal dominant optic atrophy. |
| title_sort | non image forming light driven functions are preserved in a mouse model of autosomal dominant optic atrophy |
| url | http://europepmc.org/articles/PMC3569441?pdf=render |
| work_keys_str_mv | AT georgiaperganta nonimageforminglightdrivenfunctionsarepreservedinamousemodelofautosomaldominantopticatrophy AT alunrbarnard nonimageforminglightdrivenfunctionsarepreservedinamousemodelofautosomaldominantopticatrophy AT christianakatti nonimageforminglightdrivenfunctionsarepreservedinamousemodelofautosomaldominantopticatrophy AT athanasiosvachtsevanos nonimageforminglightdrivenfunctionsarepreservedinamousemodelofautosomaldominantopticatrophy AT ronhdouglas nonimageforminglightdrivenfunctionsarepreservedinamousemodelofautosomaldominantopticatrophy AT robertemaclaren nonimageforminglightdrivenfunctionsarepreservedinamousemodelofautosomaldominantopticatrophy AT marcelavotruba nonimageforminglightdrivenfunctionsarepreservedinamousemodelofautosomaldominantopticatrophy AT sumathisekaran nonimageforminglightdrivenfunctionsarepreservedinamousemodelofautosomaldominantopticatrophy |