Asymmetrical Functional Deficits of ON and OFF Retinal Processing in the mdx(3Cv) Mouse Model of Duchenne Muscular Dystrophy

Author(s)

Tsai, Tina I. ; Salgueiro Barboni, Mirella Telles ; Nagy, Balazs Vince ; Roux, Michel J. ; Rendon, Alvaro ; Ventura, Dora Fix ; Kremers, Jan

• Document type: Journal article
• Source: INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE; v. 57, n. 13, p. 5788-5798, OCT 2016.
• Web of Science Citations: 3

Abstract

PURPOSE. The dystrophin mouse mutant mdx(3Cv) exhibits scotopic electroretinograpic (ERG) abnormalities, which resemble clinical changes observed in Duchenne muscular dystrophy (DMD) patients. In the present study, ERGs obtained from mdx(3Cv) and their wild-type littermates under scotopic, mesopic, and photopic conditions were analyzed to provide further insight on the affected retinal pathways, and to compare them with human data. METHODS. Electroretinograms of mdx(3Cv) (n = 9) and age-matched C57BL/6J mice (n = 10) included the scotopic full-field flash (for outer retinal deficits in rod pathway), scotopic threshold response (for inner retinal integrity), photopic flash, sinusoidal flicker (for outer retinal deficits in cone pathway), mesopic rapid-on/-off sawtooth flicker, and photopic long-duration flash measurements (for separate ON-/OFF-responses under different conditions). RESULTS. The mdx(3Cv) mice exhibited diminished and delayed scotopic and photopic ERGs, particularly in their b-wave and oscillatory potentials. Interestingly, homologues to the a-and b-wave of the mesopic ON-response were affected in their peak/trough times but not in their amplitude, whereas changes to both features were uncovered for photopic ON-response and sinusoidal flicker. Mesopic and photopic OFF-components were within the norm. CONCLUSIONS. Abnormal scotopic and photopic flash ERGs were observed in mdx(3Cv), which corroborate with deficits that are likely restricted to the level of photoreceptor-to-bipolar cell transmission. Further overlaps between mdx(3Cv) mice and DMD patients exist, including asymmetrical ON versus OFF ERG alterations under mesopic versus photopic vision. In mice, ON-pathway function is compromised, whereas the OFF-pathway is spared. (AU)

• FAPESP's process: 14/06457-5 - Scientific instrumentation in vision research studies at the Vision Laboratory of IPUSP
• Grantee: Dora Selma Fix Ventura
• Support Opportunities: Research Grants - Visiting Researcher Grant - International
• FAPESP's process: 12/51299-3 - International joint research on the development and application of electroretinographic and psychophysical methods for the assessment of postreceptoral on-and off-mechanisms in both chromatic and luminance retinal visual pathways in Duchenne muscular dystrophy and in Diabetes mellitus
• Grantee: Dora Selma Fix Ventura
• Support Opportunities: Regular Research Grants
• 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
• FAPESP's process: 12/01115-3 - Development and application of electroretinographic and psychophysical methods for the assessment of on and off mechanisms in both chromatic and luminance visual pathways in Diabetes Mellitus and Duchenne muscular dystrophy
• Grantee: Dora Selma Fix Ventura
• Support Opportunities: Regular Research Grants