Glaucoma alters the circadian timing system.
Glaucoma is a widespread ocular disease and major cause of blindness characterized by progressive, irreversible damage of the optic nerve. Although the degenerative loss of retinal ganglion cells (RGC) and visual deficits associated with glaucoma have been extensively studied, we hypothesize that gl...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2008-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2592693?pdf=render |
| _version_ | 1811269123525574656 |
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| author | Elise Drouyer Ouria Dkhissi-Benyahya Christophe Chiquet Elizabeth WoldeMussie Guadalupe Ruiz Larry A Wheeler Philippe Denis Howard M Cooper |
| author_facet | Elise Drouyer Ouria Dkhissi-Benyahya Christophe Chiquet Elizabeth WoldeMussie Guadalupe Ruiz Larry A Wheeler Philippe Denis Howard M Cooper |
| author_sort | Elise Drouyer |
| collection | DOAJ |
| description | Glaucoma is a widespread ocular disease and major cause of blindness characterized by progressive, irreversible damage of the optic nerve. Although the degenerative loss of retinal ganglion cells (RGC) and visual deficits associated with glaucoma have been extensively studied, we hypothesize that glaucoma will also lead to alteration of the circadian timing system. Circadian and non-visual responses to light are mediated by a specialized subset of melanopsin expressing RGCs that provide photic input to mammalian endogenous clock in the suprachiasmatic nucleus (SCN). In order to explore the molecular, anatomical and functional consequences of glaucoma we used a rodent model of chronic ocular hypertension, a primary causal factor of the pathology. Quantitative analysis of retinal projections using sensitive anterograde tracing demonstrates a significant reduction (approximately 50-70%) of RGC axon terminals in all visual and non-visual structures and notably in the SCN. The capacity of glaucomatous rats to entrain to light was challenged by exposure to successive shifts of the light dark (LD) cycle associated with step-wise decreases in light intensity. Although glaucomatous rats are able to entrain their locomotor activity to the LD cycle at all light levels, they require more time to re-adjust to a shifted LD cycle and show significantly greater variability in activity onsets in comparison with normal rats. Quantitative PCR reveals the novel finding that melanopsin as well as rod and cone opsin mRNAs are significantly reduced in glaucomatous retinas. Our findings demonstrate that glaucoma impacts on all these aspects of the circadian timing system. In light of these results, the classical view of glaucoma as pathology unique to the visual system should be extended to include anatomical and functional alterations of the circadian timing system. |
| first_indexed | 2024-04-12T21:36:25Z |
| format | Article |
| id | doaj.art-1c8f0797872945ce87c06dabdd4270e7 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T21:36:25Z |
| publishDate | 2008-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1c8f0797872945ce87c06dabdd4270e72022-12-22T03:15:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-01312e393110.1371/journal.pone.0003931Glaucoma alters the circadian timing system.Elise DrouyerOuria Dkhissi-BenyahyaChristophe ChiquetElizabeth WoldeMussieGuadalupe RuizLarry A WheelerPhilippe DenisHoward M CooperGlaucoma is a widespread ocular disease and major cause of blindness characterized by progressive, irreversible damage of the optic nerve. Although the degenerative loss of retinal ganglion cells (RGC) and visual deficits associated with glaucoma have been extensively studied, we hypothesize that glaucoma will also lead to alteration of the circadian timing system. Circadian and non-visual responses to light are mediated by a specialized subset of melanopsin expressing RGCs that provide photic input to mammalian endogenous clock in the suprachiasmatic nucleus (SCN). In order to explore the molecular, anatomical and functional consequences of glaucoma we used a rodent model of chronic ocular hypertension, a primary causal factor of the pathology. Quantitative analysis of retinal projections using sensitive anterograde tracing demonstrates a significant reduction (approximately 50-70%) of RGC axon terminals in all visual and non-visual structures and notably in the SCN. The capacity of glaucomatous rats to entrain to light was challenged by exposure to successive shifts of the light dark (LD) cycle associated with step-wise decreases in light intensity. Although glaucomatous rats are able to entrain their locomotor activity to the LD cycle at all light levels, they require more time to re-adjust to a shifted LD cycle and show significantly greater variability in activity onsets in comparison with normal rats. Quantitative PCR reveals the novel finding that melanopsin as well as rod and cone opsin mRNAs are significantly reduced in glaucomatous retinas. Our findings demonstrate that glaucoma impacts on all these aspects of the circadian timing system. In light of these results, the classical view of glaucoma as pathology unique to the visual system should be extended to include anatomical and functional alterations of the circadian timing system.http://europepmc.org/articles/PMC2592693?pdf=render |
| spellingShingle | Elise Drouyer Ouria Dkhissi-Benyahya Christophe Chiquet Elizabeth WoldeMussie Guadalupe Ruiz Larry A Wheeler Philippe Denis Howard M Cooper Glaucoma alters the circadian timing system. PLoS ONE |
| title | Glaucoma alters the circadian timing system. |
| title_full | Glaucoma alters the circadian timing system. |
| title_fullStr | Glaucoma alters the circadian timing system. |
| title_full_unstemmed | Glaucoma alters the circadian timing system. |
| title_short | Glaucoma alters the circadian timing system. |
| title_sort | glaucoma alters the circadian timing system |
| url | http://europepmc.org/articles/PMC2592693?pdf=render |
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