Title:Modulation of the Immune System for the Treatment of Glaucoma
Volume: 16
Issue: 7
Author(s): Katharina Bell, Nadine von Thun und Hohenstein-Blaul, Julia Teister and Franz Grus*
Affiliation:
- Experimental and Translational Ophthalmology Mainz, Department of Ophthalmology, Medical Center of the Johannes Gutenberg University Mainz; Langenbeckstrasse 1, 55101 Mainz,Germany
Keywords:
Immunomodulation, B cells, T cells, glaucoma, neuroprotection, immune system.
Abstract: Background: At present intraocular pressure (IOP) lowering therapies are the only
approach to treat glaucoma. Neuroprotective strategies to protect the retinal ganglion cells (RGC)
from apoptosis are lacking to date. Substantial amount of research concerning the role of the
immune system in glaucoma has been performed in the recent years. This review aims to analyse
changes found in the peripheral immune system, as well as selected local changes of retina immune
cells in the glaucomatous retina.
Methods: By dividing the immune system into the innate and the adaptive immune system, a systematic
literature research was performed to find recent approaches concerning the modulation of
the immune system in the context of glaucoma. Also ClinicalTrials.gov was assessed to identify
studies with a translational context.
Results: We found that some aspects of the immune system, such as changes in antibody levels,
changes in toll like receptor signalling, T cells and retinal microglial cells, experience more research
activity than other areas such as changes in dendritic cells or macrophages. Briefly, results from
clinical studies revealed altered immunoreactivities against retinal and optic nerve antigens in sera
and aqueous humor of glaucoma patients and point toward an autoimmune involvement in glaucomatous
neurodegeneration and RGC death. IgG accumulations along with plasma cells
were found localised in human glaucomatous retinae in a pro-inflammatory environment possibly
maintained by microglia. Animal studies show that antibodies (e.g. anti- heat shock protein 60 and
anti-myelin basic protein) elevated in glaucoma patients provoke autoaggressive RGC loss and are
associated with IgG depositions and increased microglial cells. Also, studies addressing changes in
T lymphocytes, macrophages but also local immune responses in the retina have been performed
and also hold promising results.
Conclusions: This recapitulation of recent literature demonstrates that the immune system
definitely plays a role in the pathogenesis of glaucoma. Multiple changes in the peripheral innate as
well as adaptive immune system have been detected and give room for further research concerning
valuable therapeutic targets. We conclude that there still is a great need to bring together the results
derived from basic research analysing different aspects of the immune system in glaucoma to understand
the immune context of the disease. Furthermore local immune changes in the retina of
glaucoma patients still leave room for further therapeutic targets.
