Abstract
Purpose:
Elevated intraocular pressure (IOP) levels including pressure peaks and fluctuations are a main risk factor in glaucoma. However, the pathogenetic effect of an elevated IOP is still under investigation. Furthermore, the involvement of an autoimmune component, which shows complex changes of the IgG autoantibody (Aab) repertoire, has been shown. The aim of the study was to identify if intermittent and minimal-invasive IOP elevations in vivo elicit axonal damage and lead to changes of the Aab repertoire.
Methods:
10 cup suction (CSOP) and 30 loop adjusted (LAOP) oculopression IOP elevations were performed unilaterally in OD for 1 hour per manipulation during 6 weeks in Long Evans rats. Untreated and age-matched animals were used as control. After Paraphenylenediamine staining of optic nerve cross-sections, axonal damage was evaluated in a 1-5 grading scheme. Axon density was analyzed semi-automatically via customized macro in ImageJ. Blood was collected before and 6 weeks after first IOP elevation to detect alterations of Aabs against 42 antigens using reverse phase microarray.
Results:
A cumulative IOP exposure of +188.9±16 mmHg in CSOP and +737.3±9.6 mmHg in LAOP was achieved. Treated CSOP and LAOP eyes showed a significantly elevated axonal damage grade compared to control (p<0.01) and contralateral eyes (p<0.01). Axon density (as axons/0.05 mm2) was significantly decreased in treated eyes of CSOP (17505±2890, p<0.01) and LAOP (19266±2366, p<0.05) compared to control eyes (22528±2127). Additionally, a significant difference was identified between treated and contralateral eyes in CSOP (21035±3410, p<0.05) and LAOP (23144±1956, p<0.05) group. The IgG Aab repertoire showed specific changes compared to baseline time point. 6 weeks after first IOP elevation, increased immunoreactivities were observed for alpha-synuclein, calreticulin, HSP27, and NSE (all p<0.01), while decreased immunoreactivities were identified for HSP10 (p<0.01) and GFAP (p<0.05).
Conclusions:
Intermittent IOP elevations are able to provoke an axonal damage in the optic nerve. Elevation of the IOP and axonal damage might have influenced the IgG Aab repertoire of the humoral immune system, as distinct changes were observed. These innovative glaucoma animal models enable further studies to investigate the pathogenetic impact of the humoral immune system on retinal ganglion cell loss.
Keywords: 568 intraocular pressure •
555 immunomodulation/immunoregulation •
629 optic nerve