There are other possible explanations to our observation.
Photoreceptors may die through both c-Fos–dependent or –independent
pathways after light injury. However, the number of TUNEL-positive
nuclei would have been higher than that of c-Fos–positive ones if the
c-Fos–independent pathway played a significant role. Our morphometry
study does not support this possibility. It is also possible that there
is no causal relationship of c-Fos and photoreceptor cell death but
rather a coincident induction of
c-fos.
10 For
example, Hafezi et al.
6 using
c-fos − /− rd mice
showed that there was extensive photoreceptor cell death without
c-fos expression even though Rich and her
colleagues
11 observed aberrant expression of
c-fos accompanying photoreceptor cell death in the rd mouse.
Although this is possible, there is extensive documentation of a link
between the expression of
c-fos and impending cell death in
a variety of neural and nonneural tissues during development or under
pathologic conditions. For example, Estus and his
colleagues
12 revealed that
c-fos induction was
restricted to neurons undergoing chromatin condensation, a hallmark of
apoptosis, leading to the hypothesis that
c-fos is indeed
involved in the early changes of gene expression in the apoptotic
pathway. A recent study by Hafezi and his colleagues,
5 in
which
c-fos − /− transgenic mice were used, also demonstrated the requirement of
c-fos in photoreceptor cell death after photic injury. Our
observation supports a causal role for
c-fos in
light-induced photoreceptor cell death as suggested by Hafezi et
al.
5 It is also possible that
c-fos expression
may be synchronized, whereas cell death by apoptosis as shown by TUNEL
may not be synchronized, giving rise to our observed different labeling
patterns.