Research Proposals

By the end of April 2005

three research teams (at Hadassa Ein Kerem, Tel Aviv University and Ben Gurion University) agreed to take a part in studying Best diseases.

Discovering the roles of Pax6 in the development and function of the ocular pigmented epithelium

Ruth Ashery-Padan

Department of Human Genetics & Molecular Medicine, Sackler Faculty of Medicine, Tel Aviv University

Our studies focus on understanding the molecular mechanisms regulated by the transcription factor Pax6 in the development of the vertebrate eye. Pax6 gene has probably been most extensively studied with respect to eye development as it is found to be essential for eye formation in different organisms. Moreover, misexpression of Pax6 in flies and frogs induces the formation of ectopic eyes. Recently, using the Cre/loxP approach, we revealed distinct functions for Pax6 in lens and neuroretinal development in mammals. Currently we investigate the functions of Pax6 in the development of the ocular pigmented epithelium (PE). The PE differentiates to the retinal pigmented epithelium (RPE) and the PE of the iris and ciliary body. The ocular PE cells share their embryonic origin with the neuroretina and are essential for neuroretinal development and its normal function in the adult eye. Furthermore, subtypes of PE cells have been shown to have the capacity to transdifferentiate to neuroretinal cell types in mammals. Defects in any of these PE tissue types dramatically hamper ocular physiology and are associated with diseases leading to blindness in humans. Pax6 is dynamically expressed in the PE progenitors and is detected in a subtype of PE cells in the adult eye. Elucidating the role of Pax6 in the development of the PE ocular cell types is expected to reveal the molecular functions of an extremely important transcription factor for the development of the pigmented ocular cell types, which are multifunctional and indispensable for visual functions.

Group research at BGU

Shimon Ben-Shabat & Elie Beit-Yannai

Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105, Israel

Abstract

Degenerative retinal diseases with demonstrated link to lipofuscin, such as Best disease, Age-related Macular Degeneration (AMD) and Stargartd, result in a loss of vision due to deterioration of the central region of the retina (macula). Recent evidence suggests that A2E, a pyridinium bis-retinoid, compound that accumulates in the retinal pigment epithelium (RPE) during ageing, may have deleterious effects on the retina. Degradation of A2E leads to the production of reactive oxygen species (ROS), which activate apoptosis and cell damage. The goals of our group research are to gain insight into the mechanisms that underlie A2E-mediated damage to the retina and ultimately to develop novel approaches to treating degenerative retinal diseases (Best disease, AMD and Stargartd), based on inhibition of A2E-mediated toxicity.

The Researchers & their Relevant Expertise:

Dr. Ben-Shabat is a bioorganic chemist with extensive experience in bioanalytical studies and in the synthesis of compounds of pharmaceutical interest.
Dr. Beit-Yannai is a pharmacologist with expertise in free-radical-mediated damage in different diseases, particularly in ophthalmology models.