Dystrophin and the human visual system: study of the visual phenotypes of Duchenne muscular dystrophy patients

Abstract

Proposal: DMD gene products - Dp 427, Dp260, Dp140, Dp116 and DP71 - are expressed in neural tissues. Two decades ago it was found that mutations in the DMD gene leads to functional alterations in the human visual system. However it is still not completely known what type of mutations are responsible for these changes in the retinal function of patients with Duchenne and Becker muscular dystrophy. The present study will conduct a more detailed assessment of the visual system of these patients in order to correlate the DMD gene mutation with the functional deficiency.Methods: visual tests, using non-invasive instruments, will be applied to measure the activity of different visual pathways in order to verify their integrity. A portable device to generate visual stimuli and to record electrophysiological signals from the retina and from the primary visual cortex will be developed and implemented to perform the visual evaluation at locations beyond the laboratory. The analysis will establish the relationship between the genotype and the visual phenotype of these patients.Expected results: we expect to verify: i) if different types of genetic mutations in the DMD gene cause different deficiencies in the human visual system; ii) which visual pathways are more and which are less dependent of dystrophins; iii) if the visual loss is progressive iv) the efficacy of the visual tests that may be used in the future to evaluate neural condition in DMD patients and, moreover, that may be used in future gene therapies.Progress: the project will contribute to a better understanding of the pathophysiology of the retina and the visual pathways in order to clarify what are the visual mechanisms dependent on the DMD gene products. Moreover, it will be possible to develop a non-invasive clinical test that may be used in future studies. We intend to validate a portable system to evaluate the human visual system applying psychophysical and electrophysiological methods. (AU)