Endothelin B receptors contribute to retinal ganglion cell loss in a rat model of glaucoma.
Glaucoma is an optic neuropathy, commonly associated with elevated intraocular pressure (IOP) characterized by optic nerve degeneration, cupping of the optic disc, and loss of retinal ganglion cells which could lead to loss of vision. Endothelin-1 (ET-1) is a 21-amino acid vasoactive peptide that pl...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3423444?pdf=render |
| _version_ | 1818525676735561728 |
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| author | Alena Z Minton Nitasha R Phatak Dorota L Stankowska Shaoqing He Hai-Ying Ma Brett H Mueller Ming Jiang Robert Luedtke Shaohua Yang Colby Brownlee Raghu R Krishnamoorthy |
| author_facet | Alena Z Minton Nitasha R Phatak Dorota L Stankowska Shaoqing He Hai-Ying Ma Brett H Mueller Ming Jiang Robert Luedtke Shaohua Yang Colby Brownlee Raghu R Krishnamoorthy |
| author_sort | Alena Z Minton |
| collection | DOAJ |
| description | Glaucoma is an optic neuropathy, commonly associated with elevated intraocular pressure (IOP) characterized by optic nerve degeneration, cupping of the optic disc, and loss of retinal ganglion cells which could lead to loss of vision. Endothelin-1 (ET-1) is a 21-amino acid vasoactive peptide that plays a key role in the pathogenesis of glaucoma; however, the receptors mediating these effects have not been defined. In the current study, endothelin B (ET(B)) receptor expression was assessed in vivo, in the Morrison's ocular hypertension model of glaucoma in rats. Elevation of IOP in Brown Norway rats produced increased expression of ET(B) receptors in the retina, mainly in retinal ganglion cells (RGCs), nerve fiber layer (NFL), and also in the inner plexiform layer (IPL) and inner nuclear layer (INL). To determine the role of ET(B) receptors in neurodegeneration, Wistar-Kyoto wild type (WT) and ET(B) receptor-deficient (KO) rats were subjected to retrograde labeling with Fluoro-Gold (FG), following which IOP was elevated in one eye while the contralateral eye served as control. IOP elevation for 4 weeks in WT rats caused an appreciable loss of RGCs, which was significantly attenuated in KO rats. In addition, degenerative changes in the optic nerve were greatly reduced in KO rats compared to those in WT rats. Taken together, elevated intraocular pressure mediated increase in ET(B) receptor expression and its activation may contribute to a decrease in RGC survival as seen in glaucoma. These findings raise the possibility of using endothelin receptor antagonists as neuroprotective agents for the treatment of glaucoma. |
| first_indexed | 2024-12-11T06:12:06Z |
| format | Article |
| id | doaj.art-23bb21d0aa2341ffb29b5112bf5c74c7 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T06:12:06Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-23bb21d0aa2341ffb29b5112bf5c74c72022-12-22T01:18:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4319910.1371/journal.pone.0043199Endothelin B receptors contribute to retinal ganglion cell loss in a rat model of glaucoma.Alena Z MintonNitasha R PhatakDorota L StankowskaShaoqing HeHai-Ying MaBrett H MuellerMing JiangRobert LuedtkeShaohua YangColby BrownleeRaghu R KrishnamoorthyGlaucoma is an optic neuropathy, commonly associated with elevated intraocular pressure (IOP) characterized by optic nerve degeneration, cupping of the optic disc, and loss of retinal ganglion cells which could lead to loss of vision. Endothelin-1 (ET-1) is a 21-amino acid vasoactive peptide that plays a key role in the pathogenesis of glaucoma; however, the receptors mediating these effects have not been defined. In the current study, endothelin B (ET(B)) receptor expression was assessed in vivo, in the Morrison's ocular hypertension model of glaucoma in rats. Elevation of IOP in Brown Norway rats produced increased expression of ET(B) receptors in the retina, mainly in retinal ganglion cells (RGCs), nerve fiber layer (NFL), and also in the inner plexiform layer (IPL) and inner nuclear layer (INL). To determine the role of ET(B) receptors in neurodegeneration, Wistar-Kyoto wild type (WT) and ET(B) receptor-deficient (KO) rats were subjected to retrograde labeling with Fluoro-Gold (FG), following which IOP was elevated in one eye while the contralateral eye served as control. IOP elevation for 4 weeks in WT rats caused an appreciable loss of RGCs, which was significantly attenuated in KO rats. In addition, degenerative changes in the optic nerve were greatly reduced in KO rats compared to those in WT rats. Taken together, elevated intraocular pressure mediated increase in ET(B) receptor expression and its activation may contribute to a decrease in RGC survival as seen in glaucoma. These findings raise the possibility of using endothelin receptor antagonists as neuroprotective agents for the treatment of glaucoma.http://europepmc.org/articles/PMC3423444?pdf=render |
| spellingShingle | Alena Z Minton Nitasha R Phatak Dorota L Stankowska Shaoqing He Hai-Ying Ma Brett H Mueller Ming Jiang Robert Luedtke Shaohua Yang Colby Brownlee Raghu R Krishnamoorthy Endothelin B receptors contribute to retinal ganglion cell loss in a rat model of glaucoma. PLoS ONE |
| title | Endothelin B receptors contribute to retinal ganglion cell loss in a rat model of glaucoma. |
| title_full | Endothelin B receptors contribute to retinal ganglion cell loss in a rat model of glaucoma. |
| title_fullStr | Endothelin B receptors contribute to retinal ganglion cell loss in a rat model of glaucoma. |
| title_full_unstemmed | Endothelin B receptors contribute to retinal ganglion cell loss in a rat model of glaucoma. |
| title_short | Endothelin B receptors contribute to retinal ganglion cell loss in a rat model of glaucoma. |
| title_sort | endothelin b receptors contribute to retinal ganglion cell loss in a rat model of glaucoma |
| url | http://europepmc.org/articles/PMC3423444?pdf=render |
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