Complement gene expression and regulation in mouse retina and retinal pigment epithelium/choroid
Open Access
- 14 June 2011
- journal article
- Vol. 17, 1588-1597
Abstract
To understand the expression of genes involved in different complement pathways in the retina and retinal pigment epithelium (RPE)/choroid under physiologic conditions and how their expression is regulated by inflammatory cytokines. The expression of complement components of the classical pathway (CP), mannose-binding lectin (MBL) pathway, alternative pathway (AP), and terminal pathway in the retina and RPE/choroid was determined by conventional reverse transcription polymerase chain reaction (RT–PCR). The effect of inflammatory cytokines, tumor necrosis factor-alpha (TNF-α, 20 ng/ml), interleukin (IL)-6 (10 ng/ml), interferon-gamma (IFN-γ, 100 ng/ml) or lipopolysaccharides (LPS, 1 μg/ml) on the expression of these complement component genes was tested in vitro in primary cultured RPE cells and a microglial cell line (BV2 cells) and quantified by real-time RT–PCR. In the CP, complements C1qb, C1r, C1s, C2, and C4 were constitutively expressed by retina and RPE/choroid. Complement factor H and factor B of the AP as well as C3 were also detected in the retinal and RPE/choroidal tissues. In the MBL pathway, low levels of mannose-binding lectin (MBL)-associated serine protease (MASP)-1 in the retina and RPE/choroid and MASP2L in the retina were detected. Other components, including mannose-binding lectin 1 (MBL1), mannose-binding lectin 2 (MBL2), complement factor I (CFI), complement component 5 (C5) and complement factor H-related protein 1 (CFHR1), were not detected in either the retina or the RPE/choroid. The expression of CP- and AP-complement component genes in RPE and microglial cells was upregulated by interferon (IFN)-γ treatment. Treatment with TNF-α selectively upregulated the expression of C1s and C3 genes but downregulated complement factor H gene expression in RPE and microglial cells. The expression of genes involved in the MBL pathway was not affected by the inflammatory cytokines tested in this study. Retina and RPE/choroid express a variety of complement components that are involved mainly in the CP and AP. RPE and microglial cells are the main sources of retinal complement gene expression. Retinal complement gene expression is regulated by inflammatory cytokines, such as IFN-γ and TNF-α.Keywords
This publication has 47 references indexed in Scilit:
- The pivotal role of the complement system in aging and age-related macular degeneration: Hypothesis re-visitedProgress in Retinal and Eye Research, 2010
- Para-inflammation in the aging retinaProgress in Retinal and Eye Research, 2009
- Role of DAF in Protecting against T-Cell Autoreactivity that Leads to Experimental Autoimmune UveitisInvestigative Ophthalmology & Visual Science, 2009
- Identification of Novel Dendritic Cell Populations in Normal Mouse RetinaInvestigative Ophthalmology & Visual Science, 2007
- Genetic deficiency of C3 as well as CNS-targeted expression of the complement inhibitor sCrry ameliorates experimental autoimmune uveoretinitisExperimental Eye Research, 2006
- Heterogeneous populations of microglia/macrophages in the retina and their activation after retinal ischemia and reperfusion injuryExperimental Eye Research, 2005
- Control of myeloid activity during retinal inflammationJournal of Leukocyte Biology, 2003
- Chronic low level complement activation within the eye is controlled by intraocular complement regulatory proteins.2000
- Flow cytometric identification of a minority population of MHC class II positive cells in the normal rat retina distinct from CD45lowCD11b/c+CD4low parenchymal microglia.British Journal of Ophthalmology, 1995
- Differential expression of the complement regulatory proteins in the human eye.1993