Rajput, Sugandha2012-06-292012-06-292012-04-18https://hdl.handle.net/11299/126763Mentors: Sadie L. Hebert, Linda K. McLoonDuchenne muscular dystrophy (DMD) is a muscular degenerative disease that is characterized by an age-related loss of muscle mass and function (Blake et al. 2012). It is caused by a mutation in the dystrophin gene. This mutation results in the absence of the dystrophin protein - a cytoskeletal protein that plays an important role in muscle function (Blake et al. 2012). DMD patients experience decreased lower limb muscle strength and joint contractures and most often die at an early age of respiratory complications due to intercostal muscle weakness (Blake et al. 2012). Interestingly, the extraocular muscles (EOM) that function in eye movement, primary gaze position and motor fusion are functionally and morphologically spared in DMD patients (McLoon EOM chapter, Kaminski et al. 1992, Karpati et al. 1988 and Kallestad et al. 2011). No studies have been able to find why EOM are spared while limb skeletal muscles degenerate in DMD patients. We hypothesize that two differences between EOM and limb muscle contribute to the sparing of EOM in DMD. First, unlike limb muscles, EOM undergo continuous myofiber remodelling(McLoon and Wirtschafter 2002). Second, EOM and limb muscles have different requirements for their development. The transcription factor Pitx2 is required for the development of EOM but not for the development of limb muscle (Diehl et al. 2006 and Zhou et al. 2011). Retinoic acid, a derivative of vitamin A, controls the expression of Pitx2 during development. A loss of retinoic acid signaling results in absence of EOM as well (Matt et al. 2008 and Duester 2012). One way to study the role of retinoic acid signaling in the sparing of EOM could be to investigate the number of the retinoic acid receptor alpha (RARα) - positive nuclei per myofiber in EOM and tibialis anterior (TA) limb muscle . We predict that EOM would possess more RARα than limb muscle, thereby indicating that retinoic acid signaling is involved in the sparing of EOM in DMD.en-USDepartment of OphthalmologyPresentation