Agonistic β2-Adrenergic Receptor Autoantibodies Characterize the Aqueous Humor of Patients With Primary and Secondary Open-Angle Glaucoma

Abstract

PurposeAgonistic β2-adrenergic receptor autoantibodies (β2-agAAbs) were recently observed in sera of patients with ocular hypertension (OHT), primary (POAG), and secondary open-angle glaucoma (SOAG), yet not in healthy controls (HCs). It was the aim of the present study to investigate the presence of β2-agAAb in aqueous humor (AH) samples of OAG patients and to correlate these with the corresponding β2-agAAb serum data.Material and MethodsThirty-nine patients (21 male, 18 female) were recruited from the Department of Ophthalmology, University of Erlangen-Nürnberg: twenty-one POAG, 18 SOAG. Aqueous humor samples were collected during minimal invasive glaucoma surgery. Serum and AH samples were analyzed for β2-agAAb by a bioassay quantifying the beating rate of cultured cardiomyocyte (cut-off: 2 U).ResultsThirty-six of 39 (92.3%) and 34 of 39 (87.2%) of OAG patients showed a β2-agAAb in their sera and AH samples, respectively. All β2-agAAb AH-positive OAG patients were also seropositive. We also observed a β2-agAAb seropositivity in 95 and 89% of patients with POAG and SOAG, respectively. Beta2-agAAbs were seen in 86% (POAG) and 78% (SOAG) of AH samples. The β2-agAAb adrenergic activity was increased in the AH of patients with POAG (6.5 ± 1.5 U) when compared with those with SOAG (4.1 ± 1.1 U; p = 0.004). Serum β2-agAAb adrenergic activity did not differ between the cohorts [POAG (4.5 ± 1.5 U); SOAG (4.6 ± 2.1 U; p=0.458)]. No correlation of the beating rates were observed between serum and AH samples for group and subgroup analyses.ConclusionThe detection of β2-agAAb in systemic and local circulations supports the hypothesis of a direct functional impact of these agAAbs on ocular G-protein coupled receptors. The high prevalence of β2-agAAb in serum and AH samples of patients with POAG or SOAG suggests a common role of these AAbs in the etiopathogenesis of glaucoma, independent of open-angle glaucoma subtype.

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“…This molecular pathway is certainly not specific to COVID-19. Patients with glaucoma are known to display agonistic ß2-AAb, being linked to the increased IOP ( 23 , 24 ) as an unspecific immuneapheresis eliminate the functional active ß2-AAb accompanied by a decrease in IOP and/or a number of antiglaucoma eye drops ( 23 ). AT-1-AAb was reported previously in sera of patients with malignant hypertension or preeclampsia ( 25 , 26 ).…”

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“…Even in glaucoma pathogenesis, the exact pathogenesis is under investigation. There is evidence that an involvement of the autonomic system, especially the adrenergic ß2-mediated pathway might be present in dysregulation of IOP (glaucoma) [ 56 ] and capillary microcirculation (glaucoma [ 6 ] and AD), as patients with glaucoma and AD showed a seropositivity for ß2-AAb, respectively.…”

Spezifische Biomarker im Kammerwasser von Glaukompatienten

“…In a recent study, specific antibodies against the adrenergic β2-receptor were detected in the aqueous humour of POAG patients and in patients with secondary open-angle glaucoma. The authors suspected local intraocular production, since the adrenergic activity in the aqueous humour did not correlate with that in the patientsʼ serum 23 .…”

“…In a recent study, specific antibodies against the adrenergic β2receptor were detected in the aqueous humour of POAG patients and in patients with secondary open-angle glaucoma. The authors suspected local intraocular production, since the adrenergic activity in the aqueous humour did not correlate with that in the pa-tientsʼ serum [23]. Changed Protein Expression in the Aqueous Humour of Glaucoma Patients Glaucoma results in significant changes in aqueous humour protein expression, with imbalances in various cellular processes.…”

“…In einer kürzlich erschienenen Studie ließen sich spezifische Antikörper gegen den adrenergen β2-Rezeptor im Kammerwasser von POWG-Patienten und Patienten mit sekundärem Offenwinkelglaukom nachweisen. Die Autoren vermuten eine lokale Produktion im Auge, da die adrenerge Aktivität im Kammerwasser nicht mit der im Serum der Patienten korrelierte 23 .…”