Intravitreally injected triamcinolone travels to draining lymph nodes

Abstract

 

Purpose

 

Locally administered corticosteroids are very effective in the treatment of non-infectious uveitis and uveitic cystoid macular edema. The primary anti-inflammatory effect of intravitreal steroids is presumably local via effects such as decreasing cytokine production, inhibiting mononuclear cells, and affecting intrinsic cell populations within the eye. In this study, we tested the hypothesis that intravitreally administered triamcinolone acetate (TA) may travel to the local lymph nodes differentially during periods of quiescence, acute inflammation, and chronic inflammation.

 

Methods

 

Three experimental conditions were examined: (1) non-uveitic, normal rabbits, (2) acute inflammation induced by using killed Mycobacterium butyricum antigen injected intravitreally, and (3), chronic inflammation induced by immunizing animals with an intramuscularly injected emulsion of killed Mycobacterium butyricum antigen followed 2 to 3 weeks later by induction of uveitis lasting 30 days using intravitreal M. butyricum. Bilateral submandibular lymph nodes (SMLN), deep cervical lymph nodes (DCLN), superficial cervical lymph nodes (SCLN), vitreous, and aqueous specimens were obtained one day after TA was injected intravitreally into the right eyes of New Zealand white albino female rabbits in scenarios (1) and (2), and 28 days after TA injection in scenario (3). Quantitation of TA was performed using liquid chromatography-tandem mass spectrometry on homogenized samples.

 

Results

 

In non-uveitic animals, TA was found in the ipsilateral SMLN and DCLN as well as the contralateral DCLN 24 hours after TA injection. In acute uveitis, TA was found in the bilateral SCLNs and the ipsilateral DCLN, 24 hours after TA injection (48 hours after uveitis induction). In chronic uveitis, even 28 days after TA injection (29 days after uveitis induction), TA was found in the ipsilateral SCLN at higher levels than the concentration of TA found 24 hours after acute inflammation (Table 1).

 

Conclusions

 

TA is found in the draining lymph nodes after intravitreal injection. This finding has interesting implications for the mechanism of TA efficacy when used in the setting of uveitis.

 

 

Table 1. Concentration of TA in local lymph nodes (ng/mL) after intravitreal injection in normal and uveitic rabbits. LLOQ, lower limit of quantitation; NA, not available

 

Keywords: 557 inflammation • 555 immunomodulation/immunoregulation • 746 uveitis-clinical/animal model