Effects of recurring intraocular pressure elevations on the retina and the autoimmune component

Abstract

PurposeIn glaucoma, complex changes of IgG serum autoantibody (Aab) repertoire highlight the possible contribution of an autoimmune component in the pathogenesis of this neurodegenerative disease. An elevated intraocular pressure (IOP) and its fluctuations are considered as major risk factors. The aim of the study was to identify the systemic influence of fluctuations using recurring pressure peaks and drops in a glaucoma animal model.MethodsSedated male Long Evans rats experienced a unilateral, intermittent IOP manipulation using a silicone loop adjusted around the eye globe for 1 hour during 27 treatments. The pressure profile included pressure peaks to 35 and 45 mmHg and drops to a physiologic value of 8 mmHg. Contralateral (n = 12) and untreated eyes (n = 14) served as controls. Neurodegeneration was determined after paraphenylenediamine staining and Brn3a staining. Microglia activation was identified after Iba1 staining in retinal cross‐sections. Changes of serum immunoreactivities were identified using a microarray approach with a glaucoma‐specific antigen Setup.ResultsA loss of axon density (as axons/0.05 mm2) of treated eyes (19624 ± 1709) compared to contralateral (21943 ± 1510; p < 0.01) and untreated eyes (22267 ± 1408; p < 0.01) occured, which was confirmed by retinal ganglion cell count. Next to an activation of microglia, upregulated Aab reactivities for GST, transferrin, and NSE were identified in serum of treated animals in comparison to control serum.ConclusionsThis animal model including pressure peaks and drops allows the establishment of individual IOP profiles. The retina and the optic nerve sustained a significant damage and an altered autoimmune repertoire could be induced. A significant influence of recurring pressure fluctuations could be demonstrated using this sophisticated glaucoma animal model.