Voelcker Academy

Research Symposium 2011


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Joseph Pecha

Identifying Connexin 50 Gene Mutations in Microphthalmia, Anophthalmia & Coloboma

Joseph Pecha

Mentor(s): Dr. Jean X. Jiang

Gap junctions are the means of communication between adjacent cells and are extremely important in the body’s function for this reason. Gap junctions are formed from membrane proteins called connexins. Six connexins arranged in a hexagonal pattern form a hemichannel (connexon) and two adjacent hemichannels form a gap junction. Hemichannels allow cells to communicate with other nonadjacent cells, with the environment, and with their own cells (paracrine, endocrine, and autocrine signaling respectively). The gap junction network plays a vital role in normal lens development, transparency and the maintaining of metabolic homeostasis in the lens. Since the lens is avascular, blood vessels around the lens can only deliver blood to the outer cells; however, the gap junctions allow nutrients to reach the innermost cells of the lens. Previous studies show that when connexin 50 (cx50) is knocked out, microphthalmia and cataracts occur. Our preliminary data in chickens show that cleavage of connexin 50 occurs because of protease capsase-3. When the lens is exposed to oxidative stress, caspase-3 truncates connexin 50. Recently we discovered a new protease, caspase-1, which also cleaves connexin 50. What do these cleavages by the caspase cascade mean in lens development and the development of eye disorders such as coloboma, microphthalmia, and anophthalmia? Our hypothesis is that when the function of the caspase family (caspase-1,-2 and -3) is compromised by a mutation in the connexin 50 gene, abnormal development of the whole eye, specifically these three disorders, results. Several band shifts conducted upon mutation screening indicate that it is probable that this mutation causes these diseases. I conducted a mutation screening for 48 samples of human DNA from patients with coloboma, microphthalmia, and anophthalmia, in order to see if I could discover a mutation in the connexin gene that we could then link to causing these disorders.

Collaborators: Joseph Pecha, Stephanie Mattathil, Sumin Gu, PhD, and Jean X. Jiang PhD