A Novel Therapeutic Target in Inflammatory Uveitis: Transglutaminase 2 Inhibitor

• 발행기관: 대한안과학회
• 저자명: Joonhong Sohn Ju Byung Chae Sun Young Lee Soo-Youl Kim June-Gone Kim
• 간행물 정보: 『The Korean Journal of Ophthalmology』Vol.24 No.1, 29~34쪽, 전체 6쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2010.02.28

영문 초록

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.

목차

Materials and Methods

Results

Discussion

Acknowledgements

References

키워드

Endotoxin-induced uveitis Lipopolysaccharides Transglutaminases