PMID- 19269136
OWN - NLM
STAT- MEDLINE
DCOM- 20090626
LR  - 20220317
IS  - 1095-9157 (Electronic)
IS  - 0896-8411 (Print)
IS  - 0896-8411 (Linking)
VI  - 32
IP  - 2
DP  - 2009 Mar
TI  - Autoimmunity against carbonic anhydrase II affects retinal cell functions in 
      autoimmune retinopathy.
PG  - 133-9
LID - 10.1016/j.jaut.2009.02.001 [doi]
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.
FAU - Adamus, Grazyna
AU  - Adamus G
AD  - Casey Eye Institute-BRB, Department of Ophthalmology, School of Medicine, Oregon 
      Health & Science University, Portland, OR 97239, USA. adamusg@ohsu.edu
FAU - Karren, Landon
AU  - Karren L
LA  - eng
GR  - R01 EY013053/EY/NEI NIH HHS/United States
GR  - R01 EY013053-08/EY/NEI NIH HHS/United States
GR  - EY13053/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090306
PL  - England
TA  - J Autoimmun
JT  - Journal of autoimmunity
JID - 8812164
RN  - EC 4.2.1.- (Carbonic Anhydrase II)
SB  - IM
MH  - Autoimmune Diseases/*enzymology/*immunology/pathology
MH  - Autoimmunity/*immunology
MH  - Biocatalysis
MH  - Carbonic Anhydrase II/*immunology/*metabolism
MH  - Cell Line
MH  - Eye Diseases/*enzymology/*immunology/pathology
MH  - Humans
PMC - PMC2692195
MID - NIHMS108830
EDAT- 2009/03/10 09:00
MHDA- 2009/06/27 09:00
PMCR- 2010/03/01
CRDT- 2009/03/10 09:00
PHST- 2008/11/26 00:00 [received]
PHST- 2009/02/03 00:00 [revised]
PHST- 2009/02/05 00:00 [accepted]
PHST- 2009/03/10 09:00 [entrez]
PHST- 2009/03/10 09:00 [pubmed]
PHST- 2009/06/27 09:00 [medline]
PHST- 2010/03/01 00:00 [pmc-release]
AID - S0896-8411(09)00018-3 [pii]
AID - 10.1016/j.jaut.2009.02.001 [doi]
PST - ppublish
SO  - J Autoimmun. 2009 Mar;32(2):133-9. doi: 10.1016/j.jaut.2009.02.001. Epub 2009 Mar 
      6.