Small leucine-rich proteoglycans play important roles in the organization of the extracellular matrix as well as for the regulation of cell behavior; two biological processes that are essential for angiogenesis. We investigated consequences of the targeted ablation of decorin (DCN), biglycan (BGN) and fibromodulin (FMOD) genes on inflammation-induced angiogenesis in the cornea. In wild-type mice, DCN was localized exclusively to the corneal stroma, while FMOD and BGN were more prominently expressed in epithelial cells. Endothelial cells from limbus blood vessels expressed BGN and FMOD, but no DCN. However, after induction of angiogenesis by chemical cauterization, DCN was expressed in the newly formed capillaries, together with BGN and FMOD. Notably, in DCN-deficient mice, the growth of vessels was significantly diminished, whereas it did not significantly change in FMOD- or BGN-deficient animals. Moreover, blood vessels of DCN-deficient mice exhibited a similar expression level of BGN as control mice, while FMOD was increased on day 3 after injury. These results indicate that DCN, in addition to its effects on fibrillogenesis, plays a regulatory role in angiogenesis and that FMOD in endothelial cells may be able to partially substitute for DCN.
Microglial cells, members of the monocytic lineage, represent the resident immunocompetent cells of the central nervous system including the retina with its peculiarities like a double blood retinal barrier. Microglial cells invade the retina in response to naturally occurring neuronal death during embryonic development and remodelling. Resident microglial cells are extremely sensitive to changes in their microenvironment arising from either traumatic or chronic neurodegeneration, inproper wiring, hereditary diseases or infection and become rapidly activated. In their activated state, the cells undergo drastic morphological changes, upregulate a variety of receptors and secrete soluble factors, which contribute to recognition and phagocytotic cleareance of dying or malfunctioning neurons. In this review, we aim to summarise the current knowledge of microglial involvement in experimentally induced or naturally occurring retinal neurodegenerations with emphasising on mechanisms of microglia activation. Expanding on the mechanisms, we shall discuss on approaches to pharmacologically interfere with the microglial activation and neurophagy. The protagonistic role of these cells in the outcome of certain diseases may help designing microglial targeted treatments with potential benefit for neuronal survival and regeneration in clinically relevant conditions.
Based on these results it can be concluded that the action mechanism of AM is associated with modulation of classically activated macrophages into alternatively activated macrophages or macrophage cell death, probably by engaging lipid metabolism and activating the PPAR-γ pathway, consequently curtailing effector T cell functions. Apoptotic cells induced in the environment with AM support the presence and survival of such macrophages.
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