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Microvascular and cellular responses in the retina of rats with acute experimental allergic encephalomyelitis (EAE)
1Department of Anatomy and Histology, Institute of Biomedical Research, University of Sydney, NSW, Australia.
Abstract:
The microvascular and cellular responses in the retina during acute EAE were characterized using whole-mount preparations. The earliest detectable event was the accumulation of monocytes and T cells within veins on day 7 postinduction (pi). Mild breakdown of the blood-retinal barrier (BRB), activation of microglia and infiltration of monocytes and T cells into the retinal parenchyma were first evident on days 7 to 8 pi. Monocyte adhesion to the vessel wall and breakdown of the BRB were colocalized in the same vessel segments and occurred predominantly in veins. The marked difference in response observed in the retina versus the myelinated region of the optic nerve suggests that two types of inflammatory cascades are initiated. A mild response, characterised by very low numbers of T cells and monocytes and an absence of expression of MHC class II by resident microglia, is initiated when only small amounts of the encephalitogenic antigen are present in the perivascular space or associated with perivascular antigen-presenting cells. A full blown inflammatory reaction, as observed in the optic nerve, is initiated in the presence of substantial amounts of encephalitogenic antigen. This severe response is characterised by the infiltration of large numbers of CD4+, CD8+ T cells and ED1+ monocytes, and by abundant MHC class II expression by resident microglia as well as other cell types. Thus, MHC class II expression by resident microglia may be a possible effective amplifier mechanism if the encephalitogenic antigen is encountered in the tissue parenchyma.
Insights
In acute experimental autoimmune encephalomyelitis (EAE), immune cells infiltrate retinal veins early. Microglia activation and blood-retinal barrier breakdown occur, with responses varying based on antigen levels.
Area of Science:
- Neuroimmunology
- Ophthalmology
- Immunology
Background:
- Acute experimental autoimmune encephalomyelitis (EAE) is a model for multiple sclerosis.
- Understanding retinal immune responses in EAE is crucial for neuroinflammatory diseases.
Purpose of the Study:
- To characterize microvascular and cellular responses in the retina during acute EAE.
- To investigate the role of microglia and antigen presence in initiating inflammatory cascades.
Main Methods:
- Whole-mount retinal preparations were used to analyze immune cell infiltration and blood-retinal barrier (BRB) integrity.
- Immunohistochemistry and cell counting were employed to identify specific immune cell types (monocytes, T cells) and microglia activation (MHC class II expression).
Main Results:
- Monocyte and T cell accumulation in retinal veins was the earliest event (day 7 postinduction).
- Mild BRB breakdown, microglia activation, and immune cell infiltration into the retina occurred between days 7-8 postinduction, predominantly in veins.
- Two distinct inflammatory cascades were identified: a mild response in the retina with low cell infiltration and minimal MHC class II expression, and a severe response in the optic nerve with significant immune cell infiltration and abundant MHC class II expression.
Conclusions:
- Retinal immune responses in EAE are initiated early and involve microvascular changes and immune cell infiltration.
- The severity of the inflammatory response is dependent on the amount of encephalitogenic antigen encountered.
- Resident microglia expressing MHC class II may act as amplifiers of inflammation when antigen is present within the tissue parenchyma.