TY - JOUR
T1 - Autoimmunity against carbonic anhydrase II affects retinal cell functions in autoimmune retinopathy
AU - Adamus, Grazyna
AU - Karren, Landon
N1 - Funding Information:
This study was supported by grants from the NIH (EY13053 to G.A.) and unrestricted departmental funds from the Research to Prevent Blindness.
PY - 2009/3
Y1 - 2009/3
N2 - Autoantibodies against various retinal proteins, including anti-carbonic anhydrase II (CAII) autoantibodies, have been found in patients with cancer-associated retinopathy and autoimmune retinopathy without diagnosed cancer. We studied sera from retinopathy patients that showed reactivity with a 30-kDa retinal protein, which was identified as carbonic anhydrase II (CAII), and immunolabeled cells in human retina. The goal of the study was to examine whether patients' autoantibodies induce pathogenic effects on the catalytic function of CAII, which may have metabolic consequences on cell survival. Our findings revealed that anti-CAII autoantibodies have the capacity to induce cellular damage by impairing CAII cellular function through inhibiting the catalytic activity of CAII in a dose dependent manner, decreasing intracellular pH, increasing intracellular calcium, which in effect decreases retinal cell viability. The destabilized catalytic function of CAII and alterations in cytosolic pH were found very early, suggesting that autoantibodies are the inducers of apoptosis. In summary, our study showed that anti-CAII autoantibodies provoke pathogenic effects on retinal cells by decreasing cell survival by blocking the CAII cellular functions. The current experiments may facilitate better understanding the role of the immune system in retinal degeneration and help to develop better strategies for therapy of autoimmune retinopathy.
AB - Autoantibodies against various retinal proteins, including anti-carbonic anhydrase II (CAII) autoantibodies, have been found in patients with cancer-associated retinopathy and autoimmune retinopathy without diagnosed cancer. We studied sera from retinopathy patients that showed reactivity with a 30-kDa retinal protein, which was identified as carbonic anhydrase II (CAII), and immunolabeled cells in human retina. The goal of the study was to examine whether patients' autoantibodies induce pathogenic effects on the catalytic function of CAII, which may have metabolic consequences on cell survival. Our findings revealed that anti-CAII autoantibodies have the capacity to induce cellular damage by impairing CAII cellular function through inhibiting the catalytic activity of CAII in a dose dependent manner, decreasing intracellular pH, increasing intracellular calcium, which in effect decreases retinal cell viability. The destabilized catalytic function of CAII and alterations in cytosolic pH were found very early, suggesting that autoantibodies are the inducers of apoptosis. In summary, our study showed that anti-CAII autoantibodies provoke pathogenic effects on retinal cells by decreasing cell survival by blocking the CAII cellular functions. The current experiments may facilitate better understanding the role of the immune system in retinal degeneration and help to develop better strategies for therapy of autoimmune retinopathy.
KW - Autoantibody
KW - Autoimmune retinopathy
KW - Calcium
KW - Carbonic anhydrase II
KW - Retina
KW - pH
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U2 - 10.1016/j.jaut.2009.02.001
DO - 10.1016/j.jaut.2009.02.001
M3 - Article
C2 - 19269136
AN - SCOPUS:62149107035
SN - 0896-8411
VL - 32
SP - 133
EP - 139
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
IS - 2
ER -