Thrombospondin-1 as a Regulator of Corneal Inflammation and Lymphangiogenesis: Effects on Dry Eye Disease and Corneal Graft Immunology

Thrombospondin-1 (TSP-1) is a matricellular glycoprotein that belongs to a family of evolutionary highly conserved calcium-binding proteins consisting of 5 members (TSP-1-TSP-5). In the eye, TSP-1 is expressed by several ocular cell types and is also detectable in the aqueous humor and the vitreous body. So far, TSP-1 is one of the major activators of TGF beta, suggesting a strong influence on various important cellular functions and interactions such as differentiation, migration, and wound healing. TSP-1 is also a key endogenous inhibitor of hem- and lymphangiogenesis. Several lines of evidence indicate a crucial role of TSP-1 in maintaining the ocular immune and angiogenic privilege, for example, by regulating T lymphocytes and the tolerance-promoting properties of ocular antigen-presenting cells. This review discusses the role of TSP-1 in dry eye disease and corneal graft rejection through its effects on hem- and lymphangiogenesis, as well as on the underlying immune responses. Recent work will be reviewed showing by which molecular mechanism TSP-1 modulates inflammatory processes during ocular diseases. This opens potential new treatment avenues in inflammatory and (lymph)angiogenic ocular diseases

Immune response in deep cervical lymph nodes and spleen in the mouse after antigen deposition in different intracerebral sites

Brain interstitial and cerebrospinal fluid drainage into the lymphatics was studied by injections of 5 microliters of packed sheep red blood cells (SRBC) injected into the caudate nucleus, the occipital lobe, and the lateral ventricle of the brain in mice. The number of plaque-forming cells (PFC) was determined in the deep cervical lymph nodes, the axillary lymph nodes, and the spleen, and the number of PFC was compared with the response in the same tissues after intravenous immunization with 0.1 ml 10% SRBC. The weight of the deep cervical lymph nodes increased 3.0 times on day 3 after injection in the brain parenchyma compared with the weight of these nodes after intravenous immunization. The antigen-specific response peaked on day 5, 392 +/- 37 PFC/10(6) for IgG in the deep cervical lymph nodes after antigen deposition in the caudate nucleus, whereas only a minor peak in the antigen-specific response was obtained after intraventricular antigen deposition, 127 +/- 79 PFC x 10(6) for IgG on day 6. There were no increased PFC in any of the lymph nodes after intravenous immunization. The experiments show an antigen-specific response in the deep cervical lymph nodes after intracerebral antigen deposition, whereas antigens deposited in the lateral ventricles drain preferentially to the blood, with a high response in the spleen