Electrophysiological and psychophysical evaluation of ON and OFF visual pathways in Duchenne muscular dystrophy patients

Author(s)

Mirella Telles Salgueiro Barboni

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Psicologia (IP/SBD)
• Defense date: 2012-03-02

Examining board members

Dora Selma Fix Ventura; Christina Joselevitch; André Márcio Vieira Messias; Givago da Silva Souza; Walter Yukihiko Takahashi

• Advisor: Dora Selma Fix Ventura; Jan Kremers

Abstract

The dystrophin is one of the proteins that form the glycoprotein complex necessary for the integrity of the muscular fibers. Its dysfunction causes a genetic disease called the Duchenne Muscular Dystrophy (DMD) which is lethal for humans. Besides its fundamental role in the muscle tissues the dystrophin is also necessary in the physiology of the retina, in the processing of visual information. Previous studies have demonstrated asymmetric deviations in the electroretinogram (ERG) of DMDs with bigger changes to stimuli with increasing (ON pathway) than to decreasing (OFF pathway) luminance. Moreover deficiencies in color vision and contrast sensitivity have been more frequent and severe in patients having genetic alterations related to the expression of the Dp260 isoform. The aim of the present study was to apply electrophysiological and psychophysical protocols to verify the suspected alterations in DMD patients regarding the ON and OFF visual pathways and relate the results to their genotypes. 19 DMD patients (mean age = 15.2 ± 3.4 years) were tested and their results were compared to that of an age-matched control group. Fullfield ERG and spatial and temporal luminance contrast sensitivity tests were used during the examinations. Classical protocols were applied together with the ones preferentially stimulating the ON and the OFF visual pathways. The full-field ERG test consisted of six protocols: 1. Scotopic ERG, 2. Photopic ERG, 3. and 4. Mesopic ON and OFF ERG, 5. and 6. Photopic ON and OFF ERG. For the latter four protocols flicker stimuli were used with sawtooth modulation of rapid increase and slower decrease in luminance (ON) and rapid decrease and slower increase in luminance (OFF). The psychophysical evaluation comprised 1. Spatial contrast sensitivity test with sinusoidal gratings and temporal contrast sensitivity test, and 2. Contrast sensitivity tests with checkerboard stimuli with increasing (ON) and decreasing (OFF) luminance relative to the background. These latter were presented for both short (magnocellular system) and long (parvocellular system) durations. In agreement with the literature the results show reduced amplitudes in the ERGs scotopic and photopic b-waves and also impairment in the spatial and temporal contrast sensitivities. This studys novel contribution was the presentation of the alterations in both rod driven ON and OFF ERGs and solely in the cone driven ON ERG. The psychophysical analysis showed reduced contrast sensitivity in the ON protocol similar for both magno- and parvocellular oriented stimuli. In summary the encountered alterations suggest damages in the ON mechanism of the retina. The changes in spatial luminance contrast sensitivity of DMD patients are related, at least partially, to the lack of Dp260 or to the loss of the entire dystrophin (Dp427). Future studies shall investigate this in more details applying ERG protocols to stimulate magno- and parvocellular activities, and increase the number of patients to be able to determine correlations between visual dysfunctions and genetic mutations (AU)

• FAPESP's process: 07/55125-1 - Electrophysiological and psychophysical evaluation of ON and OFF visual pathways in Duchenne muscular dystrophy young patients
• Grantee: Mirella Telles Salgueiro Barboni
• Support Opportunities: Scholarships in Brazil - Doctorate