Human retinal microglia: expression of immune markers and relationship to the glia limitans
J M Provis1, P L Penfold, A J Edwards
1Save Sight and Eye Health Institute, Department of Clinical Ophthalmology, University of Sydney, Australia.
Insights
Microglia in the human retina exhibit diverse characteristics. Some paravascular microglia express higher levels of major histocompatibility complex (MHC) antigens and macrophage markers compared to other retinal microglia.
Area of Science:
- Ophthalmology
- Neuroscience
- Immunology
Background:
- Microglia, the resident immune cells of the central nervous system, play crucial roles in retinal health and disease.
- Understanding microglial heterogeneity is essential for developing targeted therapies for retinal disorders.
Purpose of the Study:
- To investigate the immunoreactivity, morphology, and glial limitans relationship of microglia in the normal human retina.
- To determine if distinct microglial subpopulations exist within the human retina based on antigen expression.
Main Methods:
- Immunogold histochemistry and electron microscopy (EM) on human retinal flatmounts and sections.
- Antibodies against CD45, major histocompatibility complex class I (MHC-I), MHC-II, and human macrophage antigens (S22) were used.
- Optical densitometry was employed to quantify antigen expression levels.
Main Results:
- All tested antibodies showed immunoreactivity, with CD45, MHC-II, and S22 providing the most consistent labeling.
- Microglia were identified in perivascular spaces and retinal parenchyma, with some paravascular microglia closely associated with the glia limitans.
- Paravascular microglia displayed higher MHC antigen levels and S22 antigen positivity compared to non-vessel associated parenchymal microglia.
- Approximately 10% of microglia were immunoreactive for human macrophage (S22) antigens, suggesting microglial heterogeneity.
Conclusions:
- Human retinal microglia represent a heterogeneous population with distinct subpopulations.
- Paravascular microglia, associated with the glia limitans, exhibit unique immunological profiles compared to other retinal microglia.
- These findings contribute to understanding microglial diversity and their potential roles in retinal immunity.
Abstract:
The immunoreactivity, morphology and relationship to the glia limitans of microglia were investigated in flatmounts and sections of normal human retina, using immunogold histochemistry, electron microscopy (EM), and antibodies directed against CD45, major histocompatability complex class I (MHC-I), MHC-II, and human macrophage antigens. Immunoreactivity was evident for all antibodies tested, including MHC-I, which labeled both microglia and retinal vascular endothelium. Most consistent labeling was obtained using antibodies to CD45, MHC-II, and anti-human macrophage (S22) antigen. Immunoreactive cells were seen in the perivascular space (perivascular cells), where they were closely adherent to the vessel profile, and in the retinal parenchyma (microglia). Some parenchymal microglia were also vessel associated and by EM were seen to be closely related to the glia limitans (paravascular microglia). Paravascular microglia were shown by optical densitometry, to express higher levels of MHC antigens than neighboring, non-vessel associated, parenchymal microglia. In addition, paravascular microglia were macrophage (S22) antigen positive, while other parenchymal microglia did not express macrophage antigens. Quantitative data indicate that similar populations of microglia are immunoreactive to CD45, MHC-I, and MHC-II, while relatively few microglia (approximately 10%) are immunoreactive for human macrophage (S22) antigens, supporting previous suggestions that microglia are a heterogeneous population.
