PUBLICATION
Wild-type cone photoreceptors persist despite neighboring mutant cone degeneration
- Authors
- Lewis, A., Williams, P., Lawrence, O., Wong, R.O., and Brockerhoff, S.E.
- ID
- ZDB-PUB-100112-21
- Date
- 2010
- Source
- The Journal of neuroscience : the official journal of the Society for Neuroscience 30(1): 382-389 (Journal)
- Registered Authors
- Brockerhoff, Susan, Lawrence, Owen, Lewis, Alaron
- Keywords
- none
- MeSH Terms
-
- Retinal Cone Photoreceptor Cells/cytology*
- Retinal Cone Photoreceptor Cells/physiology*
- Retinal Degeneration/genetics*
- Retinal Degeneration/pathology*
- Retinal Degeneration/physiopathology
- Mutation/physiology*
- Animals
- Cell Death
- Bystander Effect/physiology
- Zebrafish Proteins/physiology
- Zebrafish
- PubMed
- 20053919 Full text @ J. Neurosci.
Citation
Lewis, A., Williams, P., Lawrence, O., Wong, R.O., and Brockerhoff, S.E. (2010) Wild-type cone photoreceptors persist despite neighboring mutant cone degeneration. The Journal of neuroscience : the official journal of the Society for Neuroscience. 30(1):382-389.
Abstract
In many retinal diseases, the malfunction that results in photoreceptor loss occurs only in either rods or cones, but degeneration can progress from the affected cell type to its healthy neighbors. Specifically, in human and mouse models of Retinitis Pigmentosa the loss of rods results in the death of neighboring healthy cones. Significantly less is known about cone-initiated degenerations and their affect on neighboring cells. Sometimes rods remain normal after cone death, whereas other patients experience a loss of scotopic vision over time. The affect of cone death on neighboring cones is unknown. The zebrafish is a cone-rich animal model in which the potential for dying cones to kill neighboring healthy cones can be evaluated. We previously reported that the zebrafish cone phosphodiesterase mutant (pde6c(w59)) displays a rapid death of cones soon after their formation and a subsequent loss of rods in the central retina. In this study we examine morphological changes associated with cone death in vivo in pde6c(w59) fish. We then use blastulae transplantations to create chimeric fish with a photoreceptor layer of mixed wild-type (WT) and pde6c(w59) cones. We find that the death of inoperative cones does not cause neighboring WT cone loss. The survival of WT cones is independent of transplant size and location within the retina. Furthermore, transplanted WT cones persist at least several weeks after the initial death of dysfunctional mutant cones. Our results suggest a potential for the therapeutic transplantation of healthy cones into an environment of damaged cones.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping