NO is a recently recognized gaseous messenger molecule. Current evidence indicates that, in the central nervous system, NO is produced enzymatically by NO synthase (NOS). In postsynaptic cells NO can be formed in response to activation of excitatory amino acid receptors. NO can then diffuse out to act on neighboring cells. NO could also be formed in presynaptic cells and thus act as a neurotransmitter in some cases. A major action of NO is to activate soluble guanylate cyclase and thus raise cGMP concentrations in target cells. NOS has been localized in various types of retinal cells. Exogenous applied NO donors have been shown to modulate cGMP-gated channels in photoreceptors, ON bipolar and ganglion cells. NO also increases Ca2+ currents in rods by a cGMP- independent mechanism. These results indicate that NO could mediate synaptic transmission between retinal neurons. It is of interest to identify the physiological roles of NO and the mechanisms by which NO modulates the visual signals. Biochemical and electrophysiological experiments will be performed on vertebrate whole retina, retinal slice and isolated neurons to: 1. Characterize the NOS activity and NO induced cGMP changes in whole retina. 2. Identify the intracellular mechanisms by which NO may modulate cellular functions. 3. Characterize NO-induced effects on bipolar-ganglion cell synaptic transmission.
