Abstract
Purpose :
Glaucoma is known as multifactorial neurodegenerative disorder. Next to an increased intraocular pressure in patients with open-angle glaucoma (OAG), a vascular dysregulation features the clinical characteristics of patients with normal tension glaucoma (NTG). As it is known that autoimmune phenomena interplay in this complex pathophysiology, it was the aim of the present study to investigate functional autoantibodies (fAAb) in sera and aqueous humor (AH) of patients with NTG and OAG.
Methods :
Thirty-six patients were recruited from the Department of Ophthalmology, University of Erlangen-Nürnberg and Eye Clinic Wittenbergplatz, Berlin: 20 OAG (sera n=20, AH n=20), 16 NTG (sera n=10, AH n=6). AH samples were collected during cataract surgery. fAAb were analyzed by a frequency modulation of an established rat cardiomyocyte bioassay in vitro. Read-out was defined as increase of the beating rate compared to baseline. Cut-off was 2 beats /15 sec (LU). Receptor type of fAAb was confirmed by specific blockers. The study was approved by the local ethics committee and was done in accordance with the tenets of the Declaration of Helsinki.
Results :
The present data showed that sera and AH of patients with OAG and NTG yielded an activation in the bioassay. The increased beating rate of the bioassay in patients with OAG was blocked by ICI118.551, indicating an effect mediated by ß2-adrenergic receptor (AR). Mean beating rates were 4.76±1 LU (sera) and 6.15±2 LU (AH) in OAG. In patients with NTG, this effect was blocked by the inhibitory peptide of the PARs YFLLRNP or partially inhibited by the antagonists Sch 79797 (PAR-1) or I-191 (PAR-2), indicating an effect, realized by the protease-activated receptors (PAR). Mean beating rates were 4.62±2 LU (sera) and 4.38±1 LU (AH) in NTG. Overall, a seropositivity of functional AAbs was observed in 97% (sera) and 96% (AH) of the samples.
Conclusions :
We postulate that different fAAb might feature different glaucoma characteristics. It can be hypothesized that an overstimulation of the ß2-AR pathway plays an important role in OAG. As other fAAB were identified in patients with NTG, recognizing the protease activated receptors PAR-1 and PAR-2, a further thrombogenic pathomechanism is assumed. Interestingly, PAR could be also observed in patients suffering from Raynaud syndrome. These data support our hypothesis of an involvement of fAAb against PARs in abnormal thrombogenic or vascular alterations in NTG.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.