Genetic dissection reveals two separate pathways for rod and cone regeneration in the teleost retina.
Development of therapies to treat visual system dystrophies resulting from the degeneration of rod and cone photoreceptors may directly benefit from studies of animal models, such as the zebrafish, that display continuous retinal neurogenesis and the capacity for injury-induced regeneration. Previous studies of retinal regeneration in fish have been conducted on adult animals and have relied on methods that cause acute damage to both rods and cones, as well as other retinal cell types. We report here the use of a genetic approach to study progenitor cell responses to photoreceptor degeneration in the larval and adult zebrafish retina. We have compared the responses to selective rod or cone degeneration using, respectively, the XOPS-mCFP transgenic line and zebrafish with a null mutation in the pde6c gene. Notably, rod degeneration induces increased proliferation of progenitors in the outer nuclear layer (ONL) and is not associated with proliferation or reactive gliosis in the inner nuclear layer (INL). Molecular characterization of the rod progenitor cells demonstrated that they are committed to the rod photoreceptor fate while they are still mitotic. In contrast, cone degeneration induces both Müller cell proliferation and reactive gliosis, with little change in proliferation in the ONL. We found that in both lines, proliferative responses to photoreceptor degeneration can be observed as 7 days post fertilization (dpf). These two genetic models therefore offer new opportunities for investigating the molecular mechanisms of selective degeneration and regeneration of rods and cones.
Morris
Ann C
AC
Department of Biological Science, Florida State University, Tallahassee, Florida 32306, USA. amorris@bio.fsu.edu
Scholz
Tamera L
TL
Brockerhoff
Susan E
SE
Fadool
James M
JM
D000818:Animals; D030801:Animals, Genetically Modified; D001973:Bromodeoxyuridine; D002452:Cell Count; D049109:Cell Proliferation; D017690:Cell Transplantation / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D012038:Regeneration / Q000502:physiology*; D012160:Retina / Q000166:cytology / Q000502:physiology*; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D015027:Zebrafish / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics
C519667:Nr2e3 protein, zebrafish; D018160:Receptors, Cytoplasmic and Nuclear; D029961:Zebrafish Proteins; D001973:Bromodeoxyuridine