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. 2000 Feb;84(2):205–211. doi: 10.1136/bjo.84.2.205

Apoptosis is a prominent feature of acute anterior uveitis in the Fischer 344 rat

J Smith 1, P Hart 1, S Standfield 1, D Coster 1, S Wing 1, K Williams 1
PMCID: PMC1723389  PMID: 10655199

Abstract

AIMS—To examine the hypothesis that apoptosis of infiltrating cells contributes to spontaneous resolution of uveitis in clinically relevant rodent models.
METHODS—Experimental melanin induced uveitis (EMIU) was induced in Fischer 344 rats by immunisation with 250 µg bovine ocular melanin. Endotoxin induced uveitis (EIU) was induced by injection of 200 µg Escherichia coli lipopolysaccharide. Formalin fixed, paraffin embedded ocular cross sections were stained by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate biotin nick end labelling (TUNEL) to identify apoptotic cells. Indirect immunoperoxidase staining of paraformaldehyde lysine periodate fixed tissue cross sections was used to demonstrate expression of inducible nitric oxide synthase (iNOS).
RESULTS—TUNEL positive mononuclear cells were observed in the anterior uvea during both EMIU and EIU at all selected time points. However, whereas the majority of mononuclear cells appeared apoptotic from the outset of disease, neutrophils were notably TUNEL negative at all time points examined. Many infiltrating neutrophils expressed iNOS.
CONCLUSION—Apoptosis occurs early in the course of rat EMIU and EIU, and may contribute to resolution of these diseases. In general, infiltrating mononuclear cells die rapidly, while neutrophils survive, producing inducible nitric oxide synthase which may contribute to disease pathogenesis.



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Figure 1  .

Figure 1  

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Sections of a Fischer 344 rat eye during early EMIU (at time of disease onset), stained by TUNEL. (A) Ciliary body, negative control: no biotinylated dUTP. (B) Ciliary body, test, showing many TUNEL positive (apoptotic) mononuclear cells. (C) Anterior chamber, test, showing TUNEL positive mononuclear cells and TUNEL negative neutrophils. Haematoxylin counterstain. Magnification ×1400.

Figure 2  .

Figure 2  

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Photomicrograph demonstrating TUNEL positive mononuclear cells and TUNEL negative polymorphonuclear cells in the aqueous exudate of a Fischer 344 rat with EIU, 24 hours after lipopolysaccharide injection. (A) Negative control: no biotinylated dUTP; (B) TUNEL test run. Haematoxylin counterstain. Magnification ×1400.

Figure 3  .

Figure 3  

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Photomicrograph of an inflamed ankle joint from a DA rat with adjuvant arthritis, showing very few TUNEL positive infiltrating cells. (A) Negative control: no biotinylated dUTP; (B) TUNEL test run. Haematoxylin counterstain. Magnification ×1400.

Figure 4  .

Figure 4  

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Photomicrograph demonstrating iNOS in cells in the anterior uvea and aqueous exudate of a F344 rat at the onset of EMIU. (A) Negative control: SAL5; (B) anti-iNOS antibody. Immunoperoxidase stain with haematoxylin counterstain. Magnification ×1400.   

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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