The role of complement in ocular pathology

Functionally active complement system and complement regulatory proteins are present in the normal human and rodent eye. Complement activation and its regulation by ocular complement regulatory proteins contribute to the pathology of various ocular diseases including keratitis, uveitis and age-related macular degeneration. Furthermore, a strong relationship between age-related macular degeneration and polymorphism in the genes of certain complement components/complement regulatory proteins is now well established. Recombinant forms of the naturally occurring complement regulatory proteins have been exploited in the animal models for treatment of these ocular diseases. It is hoped that in the future recombinant complement regulatory proteins will be used as novel therapeutic agents in the clinic for the treatment of keratitis, uveitis, and age-related macular degeneration

Transglutaminase-catalyzed incorporation of [2,5-3H]histamine into a Mr 84000 particulate protein in pancreatic islets

Rat pancreatic islet homogenates catalyze the incorporation of [2,5-3-H]histamine into endogenous proteins recovered in both the stacking gel and a Mr 84000 protein separated by polyacrylamide electrophoresis. The labelling of these proteins represents a Ca2+-dependent process inhibited by glycine methylester, but not sarcosine methylester, and enhanced after preincubation of the islets at a high concentration of D-glucose. Although transglutaminase activity is found in both soluble and particlate subcelluler fractions, the endogenous transglutaminase substrates were located mainly in paarticulate, possibly membrane-associated, material. © 1989 Plenum Publishing Corporation.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Tears contain the complement regulator CD59 as well as decay-accelerating factor (DAF)

Previous studies have shown that DAF (or CD55), a cell surface inhibitor of autologous C3 activation, is present in tears and that >90% of the C3 convertase regulatory activity in tear fluid resides in this protein (Lass JH et al., Invest Ophth Vis Sci 1990; 31:1136–48). This study investigated whether (i) the membrane cofactor protein (MCP or CD46), an additional factor that regulates C3 activation, and (ii) the membrane inhibitor of reactive lysis (MIRL or CD59), a cell surface regulator that acts to prevent formation of the membrane attack complex, are also present in tears, and if so, are functional. Two-site immunoradiometric assays showed that MCP is present in tears at low levels (42 + 8 ng/ml, n = 8) while CD59 is present at levels (222 + 78 ng/ml, n = 14) comparable to those of DAF (325 + 289 ng/ml, n = 12). The concentrations of CD59 (i) were increased two-fold or more in closed eye tears, and (ii) were decreased in reflex tears. Western blotting showed that CD59 protein in tears migrates with an apparent mol. wt similar to membrane CD59 protein. Phenyl–Sepharose adsorption and Triton X-114 partitioning of tear CD59 as well as of tear DAF however, showed that both proteins are devoid of GPI anchors. Assays using cobra venom factor-activated human serum and guinea pig erythrocytes showed that CD59 is functionally active in inhibiting autologous C5b-9-mediated lysis and, under constitutive conditions, accounts for >85% of the C9 inhibitory activity in tear fluid