Cone dystrophies and GUCA1A mutations

Cone dystrophy (COD) is a severe form of retinal disorder affecting photoreceptors, the cells where the visual signal originates. COD leads to decreased central and color vision and photophobia and in several COD patients cone dysfunction is often followed by the degeneration of rods, another type of photoreceptor. As a consequence, the evolution of the disease may result also in the progressive loss in peripheral vision. Currently, no cure exists for these diseases, which affect 1 in 10,000 people. In the last years an increasing number of genetic modifications have been identified in the gene responsible for the production of GCAP1, a sensor protein detecting intracellular calcium and regulating important biological processes. The consequence of alterations in GCAP1 have been only partly explored and mechanisms leading to the onset of the disease remain largely unclear. In this project we will characterize GCAP1 variants associated with COD by applying experimental approaches and computer simulations.

GOALS

  • Compare structural and functional properties in normal and disease-associated forms of GCAP1 and unveil the alterations in the interaction with the guanylate cyclase
  • Identify novel molecules capable of dampening and possibly eliminating the mis-regulation induced by altered GCAP1
  • Test the therapeutic potential of the newly identified molecules by making use of a suitable animal model of disease.

Collaborations


FUNDING

This project is supported by Fondazione Telethon (Grant: GGP16010, PI: Daniele Dell'Orco)