Mapping retinal degeneration and loss-of-function in Rd-FTL mice.
OBJECTIVE
Retinitis pigmentosa (RP) is a blinding disease caused by the degeneration of photoreceptors. To further understand the process of degeneration in RP, the authors have traced activation patterns associated with rod and cone photoreceptor degeneration in a mouse model of RP METHODS: The authors used a double-mutant mouse, Rd-FTL, which contains a natural mutation, rd1, affecting the rod photoreceptors and an axon-targeted beta-galactosidase reporter system, which is under the regulation of the promoter of the c-fos gene. These mice allowed the authors to trace degeneration-related activity that corresponded to rod and cone death.


RESULTS
The authors traced cell death-associated activation in both rods and cones, allowing them to accurately determine the time course of cone degeneration in these mice. In the analysis of downstream activation patterns in the inner retina, they found that amacrine and ganglion cells maintain their photopic light-related activation until at least the initiation of cone degeneration. These cell populations then show increased activity during the peak time of cone cell degeneration. The authors also examined light-regulated functional activation of a subclass of amacrine cells, the dopaminergic amacrine cells. These cells showed light-induced functional activation after rod photoreceptor death and until the period of cone photoreceptor death, suggesting that they can be regulated by cone photoreceptors alone.


CONCLUSIONS
These findings have helped to accurately trace the periods of photoreceptor degeneration in this model of RP and show that correct light-regulated inner retinal activation is maintained until the time of cone degeneration.
Greferath
Ursula
U
Department of Anatomy and Cell Biology, University of Melbourne, Melbourne, Victoria, Australia. u.greferath@unimelb.edu.au
Goh
Hänsel Chien
HC
Chua
Pei Ying
PY
Astrand
Elaine
E
O'Brien
Emily Elizabeth
EE
Fletcher
Erica Lucy
EL
Murphy
Mark
M
D025042:Amacrine Cells / Q000502:physiology*; D000818:Animals; D002452:Cell Count; D004195:Disease Models, Animal; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D016762:Genes, fos / Q000235:genetics; D008027:Light; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010781:Photography; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology*; D012162:Retinal Degeneration / Q000378:metabolism / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000502:physiology*; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D001616:beta-Galactosidase / Q000378:metabolism
D001616:beta-Galactosidase