Heme oxygenase-2 (HO-2) synthesizes carbon monoxide
(CO), a modulator of soluble guanylate cyclase (sGC). To
examine this signal transduction pathway in the retina,
we immunocytochemically localized HO-2, and investigated
the effects of CO on cGMP levels. In turtle, HO-2-like
immunoreactivity (-LI) was in all photoreceptors, some
amacrine cells, and in numerous bipolar and ganglion cells.
HO-2-LI colocalized with sGC activity in many cells. In
rat, HO-LI was found only in the inner retina, in ganglion
and amacrine cells. In turtle, stimulation with CO alone
primarily increased cGMP-LI in bipolar cells in the visual
streak. Stimulation with a combination of CO and nitric
oxide (NO) dramatically increased cGMP-LI throughout the
retina, in comparison to the smaller increases seen with
NO or CO alone. These data suggest that CO is an endogenous
modulator of the sGC/cGMP signaling pathway in many retinal
neurons, and can dramatically amplify NO-stimulated increases
in cGMP.