A Novel Therapeutic Target in Inflammatory Uveitis: Transglutaminase 2 Inhibitor.
- Author:
Joonhong SOHN
1
;
Ju Byung CHAE
;
Sun Young LEE
;
Soo Youl KIM
;
June Gone KIM
Author Information
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords: Endotoxin-induced uveitis; Lipopolysaccharides; Transglutaminases
- MeSH: Animals; Disease Progression; Enzyme Inhibitors/*therapeutic use; Female; GTP-Binding Proteins/*antagonists & inhibitors/*metabolism; Lipopolysaccharides; Rats; Rats, Inbred Lew; Transglutaminases/*antagonists & inhibitors/*metabolism; Uveitis/chemically induced/*enzymology/pathology
- From:Korean Journal of Ophthalmology 2010;24(1):29-34
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: Our goal was to investigate the effects of inhibition of transglutaminase 2 (TGase 2) on endotoxin-induced uveitis (EIU) METHODS: EIU was induced in female Lewis rats by single footpad injections of 200 microgram of lipopolysaccharide (LPS). TGase 2 inhibitors were administered intraperitoneally 30 minutes before and at the time of LPS administration. Rats were sacrificed 24 hours after injection, and the effects of the TGase 2 inhibitors were evaluated by the number of intraocular inflammatory cells present on histologic sections and by measuring the TGase 2 activity and TGase products in the aqueous humor (AqH). TGase 2 substrates were also assayed in AqH from uveitis patients. RESULTS: Clinical indications of EIU, the number of cells present on histologic sections, and TGase 2 activity in AqH increased in a time-dependent manner, peaking 24 hours after LPS injection. Inflammation in EIU was significantly reversed by treatment with TGase inhibitors. A 23-kDa cross-linked TGase substrate was identified in the AqH from EIU rats and uveitis patients. MALDI-TOF analysis showed that this substrate in uveitis patients was human Ig kappa chain C region. CONCLUSIONS: TGase 2 activity and its catalytic product were increased in the AqH of EIU rats. TGase 2 inhibition attenuated the degree of inflammation in EIU. Safe and stable TGase inhibitors may have great potential for the treatment of inflammatory uveitis.
