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Testing for a gap junction-mediated bystander effect in retinitis pigmentosa: secondary cone death is not altered by deletion of connexin36 from cones.
- Source :
-
PloS one [PLoS One] 2013; Vol. 8 (2), pp. e57163. Date of Electronic Publication: 2013 Feb 27. - Publication Year :
- 2013
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Abstract
- Retinitis pigmentosa (RP) relates to a group of hereditary neurodegenerative diseases of the retina. On the cellular level, RP results in the primary death of rod photoreceptors, caused by rod-specific mutations, followed by a secondary degeneration of genetically normal cones. Different mechanisms may influence the spread of cell death from one photoreceptor type to the other. As one of these mechanisms a gap junction-mediated bystander effect was proposed, i.e., toxic molecules generated in dying rods and propagating through gap junctions induce the death of healthy cone photoreceptors. We investigated whether disruption of rod-cone coupling can prevent secondary cone death and reduce the spread of degeneration. We tested this hypothesis in two different mouse models for retinal degeneration (rhodopsin knockout and rd1) by crossbreeding them with connexin36-deficient mice as connexin36 represents the gap junction protein on the cone side and lack thereof most likely disrupts rod-cone coupling. Using immunohistochemistry, we compared the progress of cone degeneration between connexin36-deficient mouse mutants and their connexin36-expressing littermates at different ages and assessed the accompanied morphological changes during the onset (rhodopsin knockout) and later stages of secondary cone death (rd1 mutants). Connexin36-deficient mouse mutants showed the same time course of cone degeneration and the same morphological changes in second order neurons as their connexin36-expressing littermates. Thus, our results indicate that disruption of connexin36-mediated rod-cone coupling does not stop, delay or spatially restrict secondary cone degeneration and suggest that the gap junction-mediated bystander effect does not contribute to the progression of RP.
- Subjects :
- Animals
Cell Death
Connexins genetics
Disease Models, Animal
Disease Progression
Gene Deletion
Gene Expression Regulation
Mice
Mice, Knockout
Retinal Cone Photoreceptor Cells pathology
Retinal Degeneration genetics
Retinal Degeneration metabolism
Retinitis Pigmentosa genetics
rho GTP-Binding Proteins deficiency
Gap Junction delta-2 Protein
Connexins metabolism
Gap Junctions metabolism
Retinal Cone Photoreceptor Cells metabolism
Retinitis Pigmentosa metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23468924
- Full Text :
- https://doi.org/10.1371/journal.pone.0057163