We can subdivide our findings in two broad sections:
1) Development
We performed an in situ hybridization screen in chick embryos for Wnt ligands that were expressed in the eye during its early development. We found that Wnt5a is expressed at the dorsal retinal pigmented epithelium of developing optic cup. We also investigated the role of cytoskeletal elements in the morphogenesis of the lens placode. Our results show that the thickened lens placode polarizes its actin-myosin cytoskeleton and concentrates RhoA-GTPases in the apical region prior to the initial placode distortion suggesting that Rho GTPases might be involved in lens morphogenesis.
In addition, Rho GTPases are also present in later stages of retinal development. Specifically, they are found in photoreceptors and in Mϋller glial cells at distinct stages of chick and mouse eye development. Similarly, we found that connexins show differential expression pattern during eye development. Whereas Cx36 and Cx43 increased their expression levels during development until they reach adult levels, Cx45 was increased in postnatal eyes, but decreased in the adult eye, suggesting that Cx45 might play a role in the establishment of retinal neural network.
2) Degeneration
We investigated the mechanisms of retinal degeneration in two model systems: C3H/HeJ rd/rd mice and light-induced degeneration. In both of these paradigms, Rac1 and its effectors PAK3 and PAK4 were increased. Moreover, Cx43, a glia-associated connexin is also increased, suggesting that both the Rho signaling pathways and that modulation of glia might play a role in neurodegenerative processes.
