Dr. MacLeish's work is directed toward understanding the functional organization of the vertebrate retina and the role of a gene, nna1, discovered by Dr. Holly Soares, in the processes of axon regeneration and Purkinje cell viability. For the retinal project, the approach is to use single, isolated cells from the adult to study functional components such as phototransduction and signal processing. One current project examines the calcium dynamics within different compartments of these cells. The techniques used are whole-cell patch clamping and optical recording using calcium-sensitive indicators. Currently, both an amphibian and a primate system are available for short and long term experiments. One possible clinical application is the use of intact isolated cells for transplantation into retinae that have lost cells due to disease or trauma with the hope of sight restoration

A separate project focuses on the trans-differentiation of the retinal pigment epithelium into neural retinal, a process that occurs in mature newts and salamanders and in embryonic chickens. Molecular markers are being developed to describe the retinal regeneration process more fully and an in vitro model system has been established to identify the primary induction event in the process. Histological, molecular biological and electrophysiological techniques are used in these studies. A long-term goal is to direct the trans-differentiation of retinal pigment epithelium cells of mammals to produce functional retina to replace diseased or damaged tissue in the adult.

For the axon regeneration and Purkinje cell viability project, the approach is to follow, or control, the expression of nna1 under specific conditions. The availability of pcd (Purkinje cell degeneration) mice in which mutations in nna1 exist, will be helpful in identifying the possible role of nna1 in specific cellular processes. In vitro models of wild type cells and tissue will also be used in deciphering the role of nna1 in axon regeneration and cell viability. The techniques of electrophysiology, optical imaging and molecular biology will be used in these studies.