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Jeong-Hyeon Sohn, Henry J. Kaplan, Hye-Jung Suk, Puran S. Bora, Nalini S. Bora; Chronic Low Level Complement Activation within the Eye Is Controlled by Intraocular Complement Regulatory Proteins. Invest. Ophthalmol. Vis. Sci. 2000;41(11):3492-3502.
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purpose. To explore the role of the complement system and complement regulatory
proteins in an immune-privileged organ, the eye.
methods. Eyes of normal Lewis rats were analyzed for the expression of
complement regulatory proteins, membrane cofactor protein (MCP),
decay-acceleration factor (DAF), membrane inhibitor of reactive lysis
(MIRL, CD59), and cell surface regulator of complement (Crry), using
immunohistochemistry, Western blot analysis, and reverse
transcription–polymerase chain reaction (RT-PCR). Zymosan, a known
activator of the alternative pathway of complement system was injected
into the anterior chamber of the eye of Lewis rats. Animals were also
injected intracamerally with 5 μl (25 μg) of neutralizing
monoclonal antibody (mAb) against rat Crry (5I2) or CD59 (6D1) in an
attempt to develop antibody induced anterior uveitis; control animals
received 5 μl of sterile phosphate-buffered saline (PBS), OX-18 (25μ
g), G-16-510E3 (25 μg), or MOPC-21 (25 μg). The role of
complement system in antibody-induced uveitis was explored by
intraperitoneal injection of 35 U cobra venom factor (CVF), 24 hours
before antibody injection. Immunohistochemical staining and sodium
dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) with
Western blot analysis were used to detect the presence of membrane
attack complex (MAC) and C3 activation products, respectively, in
normal and antibody-injected rat eyes.
results. Complement activation product MAC was present in the normal rat eye,
and intraocular injection of zymosan induced severe anterior uveitis.
The complement regulatory proteins, MCP, DAF, CD59, and Crry, were
identified in the normal rat eye. Soluble forms of Crry and CD59 were
also detected in normal rat aqueous humor. Severe anterior uveitis
developed in Lewis rats injected with a neutralizing mAb against Crry,
with increased formation of C3 split products. Systemic complement
depletion by CVF prevented the induction of anterior uveitis by
anti-Crry mAb. Intracameral injection of anti-rat CD59 (6D1), anti-rat
MHC class I antigen (OX-18), anti-rat Ig (G-16-510E3), or MOPC-21
caused no inflammatory reaction.
conclusions. The results suggest that the complement system is continuously active
at a low level in the normal eye and is tightly regulated by
intraocular complement regulatory proteins.
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