AVN Members : Dr. Andrew Waskiewicz

Waskiewicz Research Laboratory: Genetic Analyses of Pediatric Blindness

Congenital Blindness Associated with Photoreceptor Loss

Leber Congenital Amaurosis and Retinitis Pigmentosa are two early onset photoreceptor degeneration diseases, and collectively represent the most common causes of childhood blindness. Our research goal is to uncover the mechanisms that ensure photoreceptor survival. We have uncovered mutations in a crucial eye growth factor known as GDF6 (a secreted signaling protein) in this process. Recent research using zebrafish lacking Gdf6 has demonstrated a role in controlling metabolism of vitamin A in the developing eye. Currently, there are two projects underway: (1) to investigate the biochemical pathway downstream of GDF6 with a goal of understanding which components are necessary for photoreceptor survival; and (2) understanding the functions of vitamin A metabolites in early photoreceptor differentiation.

Birth Defects Caused by Maldevelopment of the early Eye

The second most prevalent cause of pediatric blindness is a spectrum of birth defects known as microphthalmia (small eye) and coloboma (open fissure). Our research laboratory is studying patients with these disorders with the goal of discovering genetic causality and understanding the role of such genes in early eye development. Our research has pinpointed roles for BMP, WNT, and SHH signaling pathways in specifying the nascent vertebrate dorsal-ventral retinal axis. Perturbations of such signaling pathways lead to profound defects in zebrafish eye morphogenesis. Furthermore, patients with microphthalmia and coloboma have mutations in members of these signaling pathways, demonstrating a critical role for each pathway. Current projects aim to understand novel causes of coloboma with studies of BMP signaling in the periphery of the eye and SHH signaling in the ventral retina.