April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Aprotinin Reduces Intraocular Inflammation in Endotoxin Induced Uveitis
Author Affiliations & Notes
  • D. Skondra
    Ophthalmology, Angiogenesis Laboratory, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
  • K. Noda
    Ophthalmology, Angiogenesis Laboratory, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
  • H. Yu
    Ophthalmology, Angiogenesis Laboratory, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
  • A. Schering
    Ophthalmology, Angiogenesis Laboratory, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
  • E. Gragoudas
    Ophthalmology, Angiogenesis Laboratory, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
  • A. Hafezi-Moghadam
    Ophthalmology, Angiogenesis Laboratory, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  D. Skondra, None; K. Noda, None; H. Yu, None; A. Schering, None; E. Gragoudas, None; A. Hafezi-Moghadam, None.
  • Footnotes
    Support  NIH grants HL086933 and AI050775, Massachusetts Lions Eye Research Fund Inc., Knights Templar Eye Foundation, Marion W. and Edward F. Knight AMD Fund, and Research to Prevent Blindness.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 6046. doi:
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    • Get Citation

      D. Skondra, K. Noda, H. Yu, A. Schering, E. Gragoudas, A. Hafezi-Moghadam; Aprotinin Reduces Intraocular Inflammation in Endotoxin Induced Uveitis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6046.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Aprotinin is a broad-spectrum serine protease inhibitor. Recently we showed that aprotinin reduces retinal vascular permeability in VEGF-induced and early diabetic blood retinal barrier breakdown. Aprotinin also decreases retinal thickness and leptin expression in experimental uveitis, however, its effect on ocular inflammation remains unknown. Here, we investigate the potency of aprotinin for suppressing intraocular inflammation in endotoxin induced uveitis (EIU).

Methods: : EIU was induced by hind footpad injections of LPS (200µg) in male Lewis rats. Animals were treated with 50,000 KIU Aprotinin (5ml of Trasylol) or the equivalent volume of saline, intraperitoneally q8 hrs for 24 hrs. Intraocular inflammation was evaluated 24 hrs after LPS injection. The number of infiltrated cells and protein concentration in the aqueous humor of the anterior chamber (AC) was quantified in normal and EIU animals with or without aprotinin treatment. Retinal leukocyte adhesion was quantified using the Concanavalin A assay. Retinal vascular permeability was measured with the Evans Blue (EB) technique.

Results: : Aprotinin treatment of EIU animals significantly reduced the AC cell accumulation by 85% (n=14, p<0.01) and protein concentration by 77% (n=13, p<0.01), compared with vehicle-treated controls (n=12 and n=10 respectively), 24h after disease induction. Aprotinin significantly reduced retinal vascular leakage by 73% (n=14, n=10, p=0.01) and retinal leukocyte adhesion by 80% (n=8 and n=7 respectively, p<0.05).

Conclusions: : These data suggest that aprotinin is an effective inhibitor of ocular inflammation in experimental uveitis. Though, the underlying mechanisms are not well understood, use of protease inhibitors may become a novel therapeutic approach in treatment of acute ocular inflammation.

Keywords: uveitis-clinical/animal model • inflammation 
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