G.P.106 Immunohistochemical study of cricopharyngeal muscle in oculopharyngeal muscular dystrophy

Abstract Several studies have reported abnormalities in muscle histology of cricopharyngeal muscle (CPM) from healthy donors. However, very little is known concerning the morphological structure of this muscle that, together with the elevator eyelid muscle, represents the main muscular targets of oculopharyngeal muscular dystrophy (OPMD). OPMD is a late onset autosomal dominant inherited dystrophy due to an expansion of GCG repeats in the coding region of the ubiquitously expressed PABPN1 gene. In OPMD patients, progressive involvement of these muscles leads to dysphagia and ptosis. In this study, CPM biopsies from seven OPMD patients and five healthy individuals were investigated by histological and histochemical approaches as well as by quantitative RT-PCR analysis. Surprisingly, histological features were similar between OPMD patients and control subjects without any correlation with age: in addition to the extensive fibro-connective substitution (30–40%), all CPM showed a high variability in muscle fibre size, rimmed vacuoles, internalized nuclei, ’ragged red’ fibres and split fibres. In CPM, a higher number of satellite cells were observed as compared to other muscle, with a significant difference between control and OPMD (7% versus 12% respectively), further confirmed by increased Pax7 mRNA levels. To further evaluate the regenerative capacity of these satellite cells, OPMD and control cells were transplanted into cryodamaged tibialis anterior muscle of immunodeficient mice. This study will help us to understand the defects in muscle fibres regeneration in OPMD. Analyses on CPM are now being extended to a less affected muscle, the sternocleidomastoideus muscle (SCM) from OPMD and healthy individuals to improve our understanding of the pathophysiology of OPMD.