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A Novel Therapeutic Target in Inflammatory Uveitis: Transglutaminase 2 Inhibitor
Korean Journal of Ophthalmology ; : 29-34, 2010.
Article in English | WPRIM | ID: wpr-22610
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.
Subject(s)

Full text: Available Index: WPRIM (Western Pacific) Main subject: Rats, Inbred Lew / Uveitis / Transglutaminases / Lipopolysaccharides / Disease Progression / GTP-Binding Proteins / Enzyme Inhibitors Limits: Animals Language: English Journal: Korean Journal of Ophthalmology Year: 2010 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Rats, Inbred Lew / Uveitis / Transglutaminases / Lipopolysaccharides / Disease Progression / GTP-Binding Proteins / Enzyme Inhibitors Limits: Animals Language: English Journal: Korean Journal of Ophthalmology Year: 2010 Type: Article