CELL-CELL INTERACTIONS--DYSPLASTIC RETINAL MORPHOGENESIS

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The studies proposed in this application will test the hypothesis that cell-cell interactions are important in normal retinal morphogenesis. The primary goal is to determine the role of cell surface glycoproteins and cell adhesion molecules in dysplastic retinal rosette formation. Specific objectives addressed will be: l) to determine if manipulation of cell surface components will alter the pattern formation of developing retina; 2) to determine the degree to which retinal rosette formation can be affected by manipulation of cell surface glycoproteins or adhesion molecules. Experiments are designed to approach these objectives from several different aspects. The work will use three experimental approaches: l) intravitreal injections into embryonating chicks and neonatal rats of specific enzymes or metabolic inhibitions known to modify cell surface adhesion molecules or glycoproteins as provocative tests of membrane perturbation; 2) organ cultured avian and mammalian retina will more critically evaluate and manipulate the retinal cell surface and adhesion phenomena in a more controlled environment; 3) in vitro reaggregation studies of dissociated retina will focus on the process of rosette formation and how reaggregation can be affected by modification of the cell surface. Modification of the cell surface will be accomplished using enzymes specific for sugar moieties such as endoneuraminidase which is specific for polysialic acid on neural cell adhesion molecules, or other glycosidases acting at other sugar sties. The cell surface glycoprotein components will also be altered using metabolic inhibitors specific for N-linked glycosylation or sites of glycoprotein processing. These manipulations will be evaluated by morphological and morphometric analysis of the retina. Additional studies will determine changes in cell glycoproteins and adhesion molecules using lectin histochemistry and immunohistochemical localization of cell adhesion molecules. These studies have important implications in understanding normal and aberrant retinal developmental processes as well as understanding one of the major complications of experimental retinal transplantation (rosette formation). They have implications in general developmental neurobiology and the basic understanding of cell-cell recognition.