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

• Grant number: 16/04538-3
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2016
• End date: April 30, 2019
• Field of knowledge: Humanities - Psychology - Physiological Psychology
• Principal Investigator: Dora Selma Fix Ventura
• Grantee: Dora Selma Fix Ventura
• Host Institution: Instituto de Psicologia (IP). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Alvaro Rendon Fuentes ; Balazs Vince Nagy ; Christina Joselevitch ; Daniela Maria Oliveira Bonci ; Dora Selma Fix Ventura ; Elaine Cristina Zachi ; Francisco Max Damico ; Jan Kremers ; Marcelo Fernandes da Costa ; Michel Roux ; Mirella Telles Salgueiro Barboni

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)

Scientific publications

(16)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SALGUEIRO BARBONI, MIRELLA TELLES; DIAS, SARAH LEONARDO; SILVA, LEONARDO APARECIDO; DAMICO, FRANCISCO MAX; VIDAL, KALLENE SUMMER; COSTA, MARCELO FERNANDES; NAGY, BALAZS VINCE; KREMERS, JAN; VENTURA, DORA FIX. Correlations Between Dark-Adapted Rod Threshold Elevations and ERG Response Deficits in Duchenne Muscular Dystrophy. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, v. 62, n. 4, APR 2021. (14/26818-2, 17/16948-4, 15/22227-2, 16/04538-3)

AHER, AVINASH J.; MARTINS, CRISTIANE M. G.; BARBONI, MIRELLA T. S.; NAGY, BALAZS V.; HAUZMAN, EINAT; BONCI, DANIELA M. O.; VENTURA, DORA F.; KREMERS, JAN. Electroretinographical determination of human color vision type. JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION, v. 35, n. 4, p. B92-B99, APR 1 2018. (14/26818-2, 16/22007-5, 16/04538-3, 14/25743-9)

SALGUEIRO BARBONI, MIRELLA TELLES; HAUZMAN, EINAT; NAGY, BALAZS VINCE; GOMES MARTINS, CRISTIANE MARIA; AHER, AVINASH J.; TSAI, I, TINA; OLIVERIA BONCI, DANIELA MARIA; VENTURA, DORA FIX; KREMERS, JAN. Electrodiagnosis of dichromacy. VISION RESEARCH, v. 158, p. 135-145, MAY 2019. (14/26818-2, 16/22007-5, 16/04538-3, 14/25743-9)

BARBONI, MIRELLA T. S.; RECSAN, ZSUZSANNA; SZEPESSY, ZSUZSANNA; ECSEDY, MONIKA; NAGY, BALAZS VINCE; VENTURA, DORA F.; NAGY, ZOLTAN ZSOLT; NEMETH, JANOS. Preliminary Findings on the Optimization of Visual Performance in Patients with Age-Related Macular Degeneration Using Biofeedback Training. APPLIED PSYCHOPHYSIOLOGY AND BIOFEEDBACK, v. 44, n. 1, p. 61-70, MAR 2019. (16/04538-3, 16/22007-5)

SALGUEIRO BARBONI, MIRELLA TELLES; BUENO, CLARISSA; NAGY, BALAZS VINCE; MAIA, PATRICIA LOBO; MOREIRA VIDAL, KALLENE SUMMER; ALVES, ROSANA CARDOSO; REITER, RUSSEL J.; DO AMARAL, FERNANDA GASPAR; CIPOLLA-NETO, JOSE; VENTURA, DORA FIX. Melanopsin System Dysfunction in Smith-Magenis Syndrome Patients. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, v. 59, n. 1, p. 362-369, JAN 2018. (14/26818-2, 14/50457-0, 14/06457-5, 15/22227-2, 16/04538-3, 16/22007-5)

SALGUEIRO BARBONI, MIRELLA TELLES; SZEPESSY, ZSUZSANNA; VENTURA, DORA FIX; NEMETH, JANOS. Individual Test Point Fluctuations of Macular Sensitivity in Healthy Eyes and Eyes With Age-Related Macular Degeneration Measured With Microperimetry. TRANSLATIONAL VISION SCIENCE & TECHNOLOGY, v. 7, n. 2, MAR 2018. (16/04538-3, 16/22007-5, 14/26818-2)

SALGUEIRO BARBONI, MIRELLA TELLES; VAILLEND, CYRILLE; JOACHIMSTHALER, ANNEKA; PASSOS LIBER, ANDRE MAURICIO; KHABOU, HANEN; ROUX, MICHEL J.; VACCA, OPHELIE; VIGNAUD, LUCILE; DALKARA, DENIZ; GUILLONNEAU, XAVIER; et al. Rescue of Defective Electroretinographic Responses in Dp71-Null Mice With AAV-Mediated Reexpression of Dp71. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, v. 61, n. 2, FEB 2020. (14/26818-2, 16/22007-5, 19/00777-1, 16/04538-3)

PORTNOI BARAN, LUIZ CLAUDIO; LIMA, DIEGO DA SILVA; DA COSTA, MARCELO FERNANDES; TABARES, HEYDI SEGUNDO; DA SILVA, LEONARDO APARECIDO; DIAS, SARAH LEONARDO; ZIN, ANDREA; VENTURA, DORA FIX. Visual Acuity alterations in Congenital Zika Syndrome (CZS) children from Rio de Janeiro. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, v. 61, n. 7, p. 3-pg., 2020-06-01. (14/26818-2, 16/24631-8, 16/14793-0, 16/22007-5, 16/04538-3)

SALGUEIRO BARBONI, MIRELLA TELLES; RECSAN, ZSUZSA; SZEPESSY, ZSUZSANNA; ECSEDY, MONIKA; SZEKERES, KORNEL; MACZKO, MIKLOS; URBIN, AGNES; NAGY, BALAZS VINCE; VENTURA, DORA F.; NEMETH, JANOS. Optimization of visual performance in patients with age-related macular degeneration using biofeedback training. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, v. 59, n. 9, p. 3-pg., 2018-07-01. (16/22007-5, 16/04538-3, 14/26818-2)

BARBONI, MIRELLA TELLES SALGUEIRO; JOACHIMSTHALER, ANNEKA; ROUX, MICHEL J.; NAGY, ZOLTAN ZSOLT; VENTURA, DORA FIX; RENDON, ALVARO; KREMERS, JAN; VAILLEND, CYRILLE. Retinal dystrophins and the retinopathy of Duchenne muscular dystrophy. PROGRESS IN RETINAL AND EYE RESEARCH, v. 95, p. 25-pg., 2023-07-01. (22/00191-0, 16/04538-3)

NAGY, BALAZS VINCE; ASHMAN, ZAHRA; SALGUEIRO BARBONI, MIRELLA TELLES; PADUA, LEONARDO; MOREIRA VIDAL, KALLENE SUMMER; VENTURA, DORA FIX. Dark adaptation in Duchenne muscular dystrophy with a short protocol. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, v. 58, n. 8, p. 3-pg., 2017-06-01. (14/06457-5, 16/04538-3, 14/26818-2)

SALGUEIRO BARBONI, MIRELLA TELLES; BUENO, CLARISSA; NAGY, BALAZS; MAIA, PATRICIA LOBO; MOREIRA VIDAL, KALLENE SUMMER; ALVES, ROSANA CARDOSO; AMARAL, FERNANDA GASPAR; CIPOLLA-NETO, JOSE; VENTURA, DORA FIX. Smith-Magenis Syndrome patients show reduced melanopsin response in the pupillary light reflex. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, v. 58, n. 8, p. 4-pg., 2017-06-01. (14/26818-2, 14/50457-0, 15/22227-2, 14/06457-5, 16/04538-3)

SALGUEIRO BARBONI, MIRELLA TELLES; VAILLEND, CYRILLE; JOACHIMSTHALER, ANNEKA; LIBER, ANDRE; KHABOU, HANEN; ROUX, MICHEL J.; VIGNAUD, LUCILE; DALKARA, DENIZ; GUILLONNEAU, XAVIER; VENTURA, DORA; et al. AAV-induced re-expression of Dp71 in retinal Muller glial cells recovers electroretinographic responses in Dp71-null mice. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, v. 60, n. 9, p. 3-pg., 2019-07-01. (16/22007-5, 16/04538-3, 14/26818-2)

SALGUEIRO BARBONI, MIRELLA TELLES; NAGY, BALAZS VINCE; GOMES MARTINS, CRISTIANE MARIA; OLIVERIA BONCI, DANIELA MARIA; HAUZMAN, EINAT; AHER, AVINASH; TSAI, TINA I.; KREMERS, JAN; VENTURA, DORA FIX. L-/M-cone opponency in visual evoked potentials of human cortex. JOURNAL OF VISION, v. 17, n. 9, AUG 2017. (14/25743-9, 14/26818-2, 14/06457-5, 16/04538-3, 16/22007-5)

SALGUEIRO BARBONI, MIRELLA TELLES; PASSOS LIBER, ANDRE MAURICIO; JOACHIMSTHALER, ANNEKA; SAOUDI, AMEL; GOYENVALLE, AURELIE; RENDON, ALVARO; ROGER, JEROME E.; VENTURA, DORA FIX; KREMERS, JAN; VAILLEND, CYRILLE. Altered visual processing in the mdx52 mouse model of Duchenne muscular dystrophy. Neurobiology of Disease, v. 152, MAY 2021. (16/04538-3, 19/00777-1, 14/26818-2)

BARBONI, MIRELLA TELLES SALGUEIRO; DIAS, SARAH; SILVA, LEONARDO; DAMICO, FRANCISCO MAX; VIDAL, KALLENE SUMMER; COSTA, MARCELO FERNANDES; GROSSKLAUSS, LUIS FERNANDO; NAGY, BALAZS VINCE; KREMERS, JAN J.; VENTURA, DORA FIX. Dark adapted cone/rod thresholds and ERGs in Duchenne muscular dystrophy. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, v. 61, n. 7, p. 3-pg., 2020-06-01. (16/22007-5, 16/04538-3, 14/26818-2)