PUBLICATION

A high content, small molecule screen identifies candidate molecular pathways that regulate rod photoreceptor outer segment renewal

Authors
Campbell, L.J., West, M.C., Jensen, A.M.
ID
ZDB-PUB-180921-3
Date
2018
Source
Scientific Reports   8: 14017 (Journal)
Registered Authors
Jensen, Abigail, West, Megan
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Cyclooxygenase Inhibitors/pharmacology
  • Drug Evaluation, Preclinical
  • Eye Proteins/metabolism
  • Genes, Reporter
  • Hot Temperature
  • Metabolic Networks and Pathways
  • Rhodopsin/metabolism
  • Rod Cell Outer Segment/metabolism*
  • Signal Transduction
  • Stem Cell Niche
  • Zebrafish
  • Zebrafish Proteins/metabolism
PubMed
30228302 Full text @ Sci. Rep.
Abstract
The outer segment of the vertebrate rod photoreceptor is a highly modified cilium composed of many discrete membranous discs that are filled with the protein machinery necessary for phototransduction. The unique outer segment structure is renewed daily with growth at the base of the outer segment where new discs are formed and shedding at the distal end where old discs are phagocytized by the retinal pigment epithelium. In order to understand how outer segment renewal is regulated to maintain outer segment length and function, we used a small molecule screening approach with the transgenic (hsp70:HA-mCherryTM) zebrafish, which expresses a genetically-encoded marker of outer segment renewal. We identified compounds with known bioactivity that affect five content areas: outer segment growth, outer segment shedding, clearance of shed outer segment tips, Rhodopsin mislocalization, and differentiation at the ciliary marginal zone. Signaling pathways that are targeted by the identified compounds include cyclooxygenase in outer segment growth, γ-Secretase in outer segment shedding, and mTor in RPE phagocytosis. The data generated by this screen provides a foundation for further investigation of the signaling pathways that regulate photoreceptor outer segment renewal.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes