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KMID : 0213520100240010029
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Korean Journal of Ophthalmology
2010 Volume.24 No. 1 p.29 ~ p.34
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A Novel Therapeutic Target in Inflammatory Uveitis: Transglutaminase 2 Inhibitor
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Sohn Joon-Hong
Cha Ju-Byung
Lee Sun-Young
Kim Soo-Youl
Kim June-Gone
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Abstract
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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 μg 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.
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KEYWORD
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Endotoxin-induced uveitis, Lipopolysaccharides, Transglutaminases
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