Longitudinal Analysis of Serum Autoantibody-Reactivities in Patients with Primary Open Angle Glaucoma and Optic Disc Hemorrhage

Abstract

BackgroundThe aim of our current investigation was to analyze the autoantibody-reactivities of primary open angle glaucoma patients with optic disc hemorrhage as possibly correlated to disease progression by means of a protein microarray approach.MethodsSera of patients with primary open angle glaucoma and optic disc hemorrhage (n = 16) were collected directly after study inclusion (0 weeks) and after 2 weeks, 4 weeks and 12 weeks. As a control group patients with primary open angle glaucoma (n = 18) were used (0 weeks and 12 weeks). Microarrays were incubated and occurring antibody-antigen-reactions were visualized with fluorescence labeled anti-human-IgG secondary antibodies. To detect changes in autoantibodies spot intensities were digitized and compared.ResultsWith respect to the immunoreactivity at 0 weeks level increment of anti-adaptor protein 1 complex subunit mu-1 antibodies and anti-SPRY domain-containing SOCS box protein 3 antibodies in sera of primary open angle patients with optic disc hemorrhage was detected. Linear trend analysis revealed a positive correlation with r ≥ 0.8 between antibody-level and time course. Control group show no relevant changes in the same period. Significant changes were found in time point 4 comparison between patient groups in anti-adaptor protein 1 complex subunit mu-1-level (p = 0.01). No significant changes in visual acuity were found.ConclusionWith this approach we were able to detect autoimmune reactivities in sera of patients with primary open angle glaucoma and optic disc hemorrhage compared to patients without optic disc hemorrhage. These antibodies could give further insights into the pathogenesis and the autoimmune component of glaucomatous optic neuropathy.

Neuroinflammatory Mechanisms of Mitochondrial Dysfunction and Neurodegeneration in Glaucoma

“…In line with these results, a longitudinal study revealed a gradual increment of serum autoantibodies in glaucoma patients with optic disc hemorrhages and no detectable change in patients with no optic disc hemorrhages [217]. In addition, the transfer of mononuclear cells from patients with optic disc hemorrhages into immune-deficient mice resulted in increased RGC loss [145,217]. e tracing of circulating monocytes with an inflammatory profile in the DBA/2J model confirmed the entry of these cells into the ONH and its contribution to glaucomatous damage [17].…”

“…Breaches in the blood-retina barrier may become visible and result in small optic disc hemorrhages or parapapillary chorioretinal atrophy areas, both of which are commonly detectable in glaucomatous eyes [ 215 , 216 ]. In line with these results, a longitudinal study revealed a gradual increment of serum autoantibodies in glaucoma patients with optic disc hemorrhages and no detectable change in patients with no optic disc hemorrhages [ 217 ]. In addition, the transfer of mononuclear cells from patients with optic disc hemorrhages into immune-deficient mice resulted in increased RGC loss [ 145 , 217 ].…”

Immunomodulation as a Neuroprotective Strategy for Glaucoma Treatment

“…Interestingly, activated microglia have been found strategically positioned within the regions of parapapillary chorioretinal atrophy in glaucomatous eyes [26,27]. A longitudinal study of serum autoantibody reactivity has also showed an increase over time in glaucoma patients with optic disc hemorrhages, but no change has been detected in patients without optic disc hemorrhages [97]. Consistent with these observations, transfer of the mononuclear cells obtained from glaucoma patients with optic disc hemorrhages into immune deficient mice has resulted in a marked decrease in RGC density (presented at the Annual Meeting of the Association for Research in Vision and Ophthalmology, 2018, Abstract # 3731).…”