Blockage of complement regulators in the conjunctiva and within the eye leads to massive inflammation and iritis.
The open environment of the eye is continuously subject to an influx of foreign agents that can activate complement. Decay-accelerating factor (DAF), membrane cofactor protein (MCP) and CD59 are regulators that protect self-cells from autologous complement activation on their surfaces. They are expressed in the eye at unusually high levels but their physiological importance in this site is unstudied. In the rat, a structural analogue termed 5I2 antigen (5I2 Ag) has actions overlapping DAF and MCP. In this investigation, we injected F(ab')2 fragments of 5I2 mAb into the conjunctiva and aqueous humor, in the latter case with and without concomitant blockage of CD59. Massive neutrophilic infiltration of the stroma and iris resulted upon blocking 5I2 Ag activity. Frank necrosis of the iris occurred upon concomitant intraocular blockage of CD59. C3b was identified immunohistochemically, and minimal effects were seen in complement-depleted animals and in those treated with non-relevant antibody. The finding that blockage of 5I2 Ag function in periocular tissues and within the eye causes intense conjunctival inflammation and iritis demonstrates the importance of intrinsic complement regulators in protecting ocular tissues from spontaneous or bystander attack by autologous complement.
Bardenstein
D S
DS
Institute of Pathology, Center for Vision Research, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Cheyer
C J
CJ
Lee
C
C
Cocuzzi
E
E
Mizuno
M
M
Okada
N
N
Medof
M E
ME
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface; D018957:CD59 Antigens / Q000276:immunology; D003167:Complement Activation / Q000276:immunology*; D003228:Conjunctiva / Q000276:immunology; D003231:Conjunctivitis / Q000276:immunology* / Q000473:pathology; D005123:Eye / Q000276:immunology*; D007108:Immune Tolerance; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007500:Iritis / Q000276:immunology* / Q000473:pathology; D051379:Mice; D020556:Neutrophil Infiltration / Q000276:immunology; D051381:Rats; D011956:Receptors, Cell Surface; D011951:Receptors, Complement / Q000037:antagonists & inhibitors* / Q000276:immunology; D017463:Receptors, Complement 3b
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D018957:CD59 Antigens; C081470:Cr1l protein, mouse; C513105:Cr1l protein, rat; D007140:Immunoglobulin Fab Fragments; D011956:Receptors, Cell Surface; D011951:Receptors, Complement; D017463:Receptors, Complement 3b