Abstract
Purpose :
Pseudoexfoliation syndrome (PEXS) and glaucoma (PEXG) are assumed to be a general elastosis with accumulation of PEX material in ocular and extraocular tissues, yet, the exact pathophysiology is not known. PEXG, the most common type of secondary open-angle glaucoma (OAG), is characterized by large intraocular pressure (IOP) peaks with progressive visual field loss. Recently, agonistic autoantibodies (AAb) against the ß2 adrenergic receptor (AR) were shown to be present in sera of patients with primary and secondary OAG and seemed to be linked to IOP.1,2 The present study aimed to investigate the presence of agonistic and inhibitory autoantibodies directed against the ß2-AR in sera of patients with PEXS and PEXG.
Methods :
49 individuals were included: 39 patients (15 PEXG, 9 PEXS, 15 primary OAG) and 10 controls. All patients underwent standard ophthalmological examination with Octopus G1 perimetry. AAbs in serum samples were analyzed by frequency modulation of a specific rat cardiomyocyte bioassay in vitro. Identification of the interacting loop of the ß2-AR and immunoglobulin G analysis were done. The study was approved by the local ethics committee and was done in accordance with the tenets of the Declaration of Helsinki. Informed consent was achieved.
Results :
Serum samples of controls were ß2-AAb negative (0.16±0.5 beats/15 sec). No agonistic ß2-AAb (0.24±0.4 beats/15 sec), yet inhibitory ß2-AAb (after additional incubation with 3 µM clenbuterol: 5.84±1.7 beats/15 sec), were observed in 80% of PEXS patients, partially blocking the clenbuterol effect (11.10±0.9 beats/15 sec). Loop analysis showed that inhibitory ß2-AAb were directed against the 3rd extracellular loop of β2-AR. Additionally, they were of IgG3 subtype in PEXS patients. Contrary, PEXG patients showed agonistic ß2-AAb (5.62±0.9 beats/15 sec), yet no inhibitory ß2-AAb. The beating rate was not significantly different between PEXG and POAG patients (3.89±2.8 beats/15 sec; p>0.05). Even synergistic ß2-AAb were observed in sera of 2 PEXG patients (after additional incubation with 1µM clenbuterol: 16.33±0.9 beats/15 sec), overtopping single incubation with 1µM clenbuterol (11.5±0.3 beats/15 sec).
Conclusions :
As autoimmune mechanisms were observed to be involved in glaucoma pathogenesis, agonistic and inhibitory ß2-AAb seem to be a part of this multifactorial interplay.
This is a 2021 ARVO Annual Meeting abstract.