PUBLICATION
Novel Animal Model of Crumbs-Dependent Progressive Retinal Degeneration That Targets Specific Cone Subtypes
- Authors
- Fu, J., Nagashima, M., Guo, C., Raymond, P.A., Wei, X.
- ID
- ZDB-PUB-180126-10
- Date
- 2018
- Source
- Investigative ophthalmology & visual science 59: 505-518 (Journal)
- Registered Authors
- Nagashima, Mikiko, Raymond, Pamela, Wei, Xiangyun
- Keywords
- none
- MeSH Terms
-
- Aging/physiology
- Animals
- Animals, Genetically Modified
- Cell Count
- Disease Models, Animal*
- Gene Expression Regulation/physiology*
- Immunohistochemistry
- Membrane Proteins/genetics*
- Retinal Cone Photoreceptor Cells/pathology*
- Retinal Degeneration/physiopathology*
- Zebrafish
- Zebrafish Proteins/genetics*
- PubMed
- 29368007 Full text @ Invest. Ophthalmol. Vis. Sci.
Citation
Fu, J., Nagashima, M., Guo, C., Raymond, P.A., Wei, X. (2018) Novel Animal Model of Crumbs-Dependent Progressive Retinal Degeneration That Targets Specific Cone Subtypes. Investigative ophthalmology & visual science. 59:505-518.
Abstract
Purpose Human Crb1 is implicated in some forms of retinal degeneration, suggesting a role in photoreceptor maintenance. Multiple Crumbs (Crb) polarity genes are expressed in vertebrate retina, although their functional roles are not well understood. To gain further insight into Crb and photoreceptor maintenance, we compared retinal cell densities between wild-type and Tg(RH2-2:Crb2b-sfEX/RH2-2:GFP)pt108b transgenic zebrafish, in which the extracellular domain of Crb2b-short form (Crb2b-sfEX) is expressed in the retina as a secreted protein, which disrupts the planar organization of RGB cones (red, green, and blue) by interfering with Crb2a/2b-based cone-cone adhesion.
Methods We used standard morphometric techniques to assess age-related changes in retinal cell densities in adult zebrafish (3 to 27 months old), and to assess effects of the Crb2b-sfEX transgene on retinal structure and photoreceptor densities. Linear cell densities were measured in all retinal layers in radial sections with JB4-Feulgen histology. Planar (surface) densities of cones were determined in retinal flat-mounts. Cell counts from wild-type and pt108b transgenic fish were compared with both a "photoreceptor maintenance index" and statistical analysis of cell counts.
Results Age-related changes in retinal cell linear densities and cone photoreceptor planar densities in wild-type adult zebrafish provided a baseline for analysis. Expression of Crb2b-sfEX caused progressive and selective degeneration of RGB cones, but had no effect on ultraviolet-sensitive (UV) cones, and increased numbers of rod photoreceptors.
Conclusions These differential responses of RGB cones, UV cones, and rods to sustained exposure to Crb2b-sfEX suggest that Crb-based photoreceptor maintenance mechanisms are highly selective.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping