Abstract

FR.14.04

Light damage, inflammation, degeneration

Remé C.¹, Joly S.¹, Lang K.², Odermatt B.³, Beck S.⁴, Seeliger M.⁴, Samardzija M.¹, Grimm C.^1
1Laboratory Retinal Cell Biology, ²Institute of Experimental Immunology, ³Institute of Pathology, University Hospital Zurich, ⁴Retinal Diagnostics Research Group, University Hospital Tübingen

Objective: Inflammatory cells gain significance in view of genetic variants of the complement system, which dramatically increase the risk of age-related macular degeneration. Modifiers triggering inflammatory responses may further elevate risk. We investigated the origin of phagocytic cells and release of inflammatory mediators in acute light-damage.
Methods: C57BL/6 mice were lethally irradiated (950 rad) on day 1. On day 2, 8 x 106 bone marrow cells of green fluorescent protein (gfp) transgenic C57BL/6 mice were injected i.p. into irradiated recipient mice. 8 wks thereafter, mice were exosed to 30 mW/cm² blue light of 410 nm ±10 nm and recovered for various intervals. Antibodies against hematogenous and glia-derived macrophages were applied in cryostat sections from gfp-positive mouse chimeras and controls. Retinal mRNA and protein of MCP-1 (monocyte chemoattractant protein-1) were analyzed and laser scanning ophthalmoscopy was performed in vivo.
Results: Immunohistochemistry indicated hematogenous origin of macrophages. Fluorescence microscopy and laser scanning ophthalmoscopy indicated in addition activated microglia in the inner retina. MCP-1 mRNA significantly increased at 6, 12 and 24 h after exposure and protein at 24 and 36 h.
Conclusions: Data indicate hematogenous origin of macrophages in light-damage. However, gfp autofluorescence was also observed in activated microglia cells suggesting bone marrow-derived replenishment of microglia upon stimulation by apoptotoic cells and / or inflammatory cytokines. Macrophages and activated microglia may differ in their effects on apoptosis and potential immune responses. This may influence therapies to reduce deleterious effects of inflammatory reactions. Occurrence of both cell types suggests redundance for the role of phagocytosis. Further, immune privilege may not consistently protect against inflammation.

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