We are applying electron microscope (EM) tomography to the visualization of the phototransduction cascade of mouse rod photoreceptors using thin-sectioned retinas. This technique is based on the principle that the shape of macromolecular assemblies can be reconstructed by algorithms that combine the data from multiple bidimensional views at different projection angles. While EM tomography provides the spatial resolution necessary for the visualization of the critical components of the phototransduction cascade, instantaneous freezing at known millisecond intervals from termination of illumination affords the temporal resolution required to catch the dynamic molecular interactions that follow rhodopsin activation and inactivation.

By using conventional electron microscopy and high pressure freezing, we are analyzing the structure of the synapses between the endings of the olfactory neurons and their postsynaptic processes in the glomeruli of the fly antennal lobe, with a special interest in the mechanism by which synaptic vesicles are captured by the presynaptic specialization and presented to the presynaptic membrane where they undergo exocytosis.

We are seeking evidence in support of our hypothesis that in the juvenile primate the visual input modulates the release of vasoactive intestinal peptide (VIP) by a class of retinal amacrine cells. VIP is a known mitogen and it would stimulate the proliferation of the neural progenitors in the retinal periphery. If the retina is chronically presented with images without contrast, increased secretion of VIP causes excessive growth of the peripheral retina, excessive elongation of the postequatorial segment of the eye and myopia.