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A.G. Junemann, M. Herrmann, A. Sheriff, P. Stergiopoulos, U. Schlotzer–Schrehardt, F.E. Kruse, R. Kunze, G. Wallukat; Agonistic Autoantibodies Against Beta2–Adrenergic Receptors in Ocular Hypertension and Primary Open–Angle Glaucoma . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3384.
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Betablockers are a standard therapy in POAG. Therefore, the purpose of this study was to analyze whether autoantibodies (AAB) against beta2–adrenergic receptors can be detected in patients with ocular hypertension and primary open–angle glaucoma.
48 patients with primary open–angle glaucoma (POAG), 11 patients with ocular hypertension (OHT), and 19 controls were included. The autoantibodies (AAB) are diagnosed in a bioassay (1). Cultured neonatal rat cardiomyocytes are used to identify AAB directed against G–protein coupled receptors (GPCR) and to study their interaction. These cells beat spontaneously and express several GPCR. The change in the activation status of the cells can be measured directly by counting the beating rate. The specificity of the observed effects and the identification of the involved receptor type are tested by the administration of receptor specific antagonists. The ,,bioassay" for agonistic antibodies, stimulating rat cardiomyocytes is highly reproducible.
Antibodies stimulating rat cardiomyocytes via the ß2–adrenergic receptor can be found in 75% of POAG and 73% of OHT patients. The effect was highly significant in both groups (p<0.001). Stimulation of rat cardiomyocytes by AAB in POAG and OHT is sensitive for ICI, a specific ß2–adrenergic receptor blocker which actively decreases contraction through a G–protein coupled form of the ß2–adrenergic receptor. Cardiomyocytes are sensitive against the ß2–agonistic clenbuterol in the presence of negative sera. Therefore, the cardiomyocytes, which were incubated with the negative samples, worked properly. Additionally, we resolved that AAB of POAG patients stimulating rat cardiomyocytes are of IgG3 isotype.
In patients with POAG and OHT agonistic autoantibodies directed to G–protein coupled ß2–receptor were found. The findings may indicate a possible role in the aequous humor dynamics and may support autoimmune aspects of the pathogenesis of open–angle glaucoma (1) Dragun D, Muller DN, Brasen L, Fritsche L, Nieminen–Kelha M, Dechend R, Kintscher U, Rudolph B, Hoebeke J, Eckert D, Mazak I, Plehm R, Schonemann C, Unger T, Budde K, Neumayer HH, Luft FC, Wallukat G. Angiotensin II type 1–receptor activating antibodies in renal–allograft rejection. N Engl J Med 2005; 352: 558–569
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