Retinal dysfunction in patients with chronic Chagas' disease is associated to anti-Trypanosoma cruzi antibodies that cross-react with rhodopsin.
To investigate retinal involvement in chronic Chagas' disease, we performed electroretinography and retinal fluorescein angiography studies in chagasic patients. Our results demonstrated a dissociated electrophysiological response characterized by both an abnormal reduction of the electroretinographic b-wave amplitude and a delayed latency, under the dark-adaptated condition. These alterations are compatible with a selective dysfunction of the rods. Antibodies raised against Trypanosoma cruzi that also interact with beta1-adrenergic receptor blocked light stimulation of cGMP-phosphodiesterase in bovine rod membranes. The specificity from the antibody-rhodopsin interaction was confirmed by Western blot analysis and antigenic competition experiments. Our results suggest an immunomediated rhodopsin blockade. T. cruzi infection probably induces an autoimmune response against rhodopsin in the chronic phase of Chagas' disease through a molecular mimicry mechanism similar to that described previously on cardiac human beta1-adrenergic and M2-cholinergic receptors, all related to the same subfamily of G-protein-coupled receptors.
Matsumoto
Silvia C
SC
Department of Neurology, Hospital Dr. Teodoro Alvarez, Buenos Aires, Argentina.
Labovsky
Vivian
V
Roncoroni
Marcela
M
Guida
María C
MC
Giménez
Luisa
L
Mitelman
Jorge
J
Gori
Horacio
H
Jurgelevicius
Renata
R
Grillo
Alejandro
A
Manfredi
Pablo
P
Levin
Mariano J
MJ
Paveto
Cristina
C
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000502:physiology; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology*; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D002417:Cattle; D014355:Chagas Disease / Q000150:complications / Q000276:immunology*; D003429:Cross Reactions; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D011930:Reaction Time; D018342:Receptors, Adrenergic, beta-1 / Q000276:immunology; D012164:Retinal Diseases / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D017948:Retinal Rod Photoreceptor Cells / Q000276:immunology* / Q000503:physiopathology / Q000528:radiation effects; D012243:Rhodopsin / Q000276:immunology*; D012374:Rod Cell Outer Segment / Q000276:immunology; D015398:Signal Transduction / Q000528:radiation effects; D014349:Trypanosoma cruzi / Q000276:immunology*
D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D018342:Receptors, Adrenergic, beta-1; D012243:Rhodopsin; D015106:3',5'-Cyclic-GMP Phosphodiesterases