The retina of c-fos-/- mice: electrophysiologic, morphologic and biochemical aspects.
OBJECTIVE
Mice without a functional c-Fos protein (c-fos-/- mice) do not exhibit light-induced apoptotic cell death of rods in contrast to their wild-type littermates (c-fos+/+ mice). To analyze the consequences of the absence of c-fos in the retina, we investigated whether the retinas of c-fos-/- mice have a reduced capacity to absorb and transduce light compared with c-fos+/+ mice.


METHODS
Retinal function was evaluated in dark-adapted mice by full-field electroretinograms (ERGs) over more than 6 log units of intensity. Retinal morphology was studied by light- and electron microscopy. Arrestin and the heat shock protein 70 (Hsp70) were detected by Western blot analysis. The rhodopsin content and the kinetics of rhodopsin regeneration were determined in retinal extracts.


RESULTS
Although the configuration of the ERGs was comparable in both groups of mice, c-fos-/- mice showed a marked variability in all quantitative ERG-measures with lower mean amplitudes, longer latencies, and a 0.9-log-unit lower b-wave sensitivity on average. Morphometry showed that c-fos-/- mice have 23% fewer rods on average, whereas the number of cones was comparable among c-fos+/+ and c-fos-/- mice. Arrestin levels appeared slightly reduced in c-fos-/- mice when compared with c-fos+/+ mice, whereas Hsp70 levels were comparable in both genotypes. The kinetics of rhodopsin regeneration were similar, but c-fos-/- mice had a 25% lower rhodopsin content on average.


CONCLUSIONS
Compared with c-fos+/+ mice, retinal function in c-fos-/- mice is attenuated to a variable but marked degree, which may be, at least in part, related to the reduced number of rods and the reduced rhodopsin content. However, c-fos does not appear to be essential for the ability to absorb photons, nor for phototransduction or the function of second-order neurons. The resistance to light-induced apoptosis of photoreceptor cells in c-fos-/- mice may result from the acute deficit of c-fos in the apoptotic cascade rather than from developmental deficits affecting rod photoreceptor function.
Kueng-Hitz
N
N
Department of Ophthalmology, University Hospital Zurich, Switzerland.
Grimm
C
C
Lansel
N
N
Hafezi
F
F
He
L
L
Fox
D A
DA
Remé
C E
CE
Niemeyer
G
G
Wenzel
A
A
D000818:Animals; D017209:Apoptosis; D019393:Arrestin / Q000378:metabolism; D015153:Blotting, Western; D003623:Dark Adaptation / Q000502:physiology; D004596:Electroretinography; D017353:Gene Deletion; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology*; D011833:Radiation Injuries, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D012160:Retina / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D012243:Rhodopsin / Q000378:metabolism*; D014785:Vision, Ocular / Q000502:physiology*
D019393:Arrestin; D018840:HSP70 Heat-Shock Proteins; D016760:Proto-Oncogene Proteins c-fos; D012243:Rhodopsin