The molecular portfolio of the extraocular muscles

Bakgrund: The extraocular muscles (EOMs) have physiological properties that separate them from other muscles, not least their distinct behavior in disease. However, little is known concerning the molecular basis of this difference. The present project aims at identifying navel strategies relevant for the treatment of muscle dystrophies and better knowledge regarding the function of the EOMs and their response to strabismus surgery. 

Frågeställning: The specific aims are: (1) To determine the molecular portfolio of the different cell types in the human EOMs to better understand their functional specialization and behavior in strabismus, (2) To elucidate the roles of key cytoskeletal proteins and their partners at neuromuscular and myotendinous junctions in the EOMs.

Arbetsplan: This is a long-running project combining rare human donor and patient material, along with navel double and triple CRISPR/Cas9 zebrafish mutants and a variety of powerful methods (eg RNAseq, EM). We particularly focus on cytoskeletal differences in EOMs vs trunk muscles. 

Betydelse: There are no satisfactory therapeutic tools to help patients with muscular dystrophies and a large proportion of patients undergoing strabismus surgery require re-operations. The study advances our knowledge on the EOMs. We recently identified Fhl2 as a protective agent and a candidate target gene for therapy.