Issue title: Special Issue in Honour of the Editor-in-Chief Prof. Dr. Ing. Friedrich Jung on his 70th Birthday
Article type: Research Article
Authors: Arora, N.a; 1 | Caldwell, A.b; c; d; 1 | Wafa, K.b | Szczesniak, A.c | Caldwell, M.c | Al-Banna, N.b | Sharawy, N.b | Islam, S.b | Zhou, J.b | Holbein, B.E.a; e | Kelly, M.E.M.b; c | Lehmann, Ch.a; b; c; d; *
Affiliations:
[a] Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada
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[b] Department of Anesthesia, Pain Management and Perioperative Medicine, Dalhousie University, Halifax, NS, Canada
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[c] Department of Pharmacology, Dalhousie University, Halifax, NS, Canada
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[d] Department of Physiology and Biophysics, Dalhousie University, Halifax, NS, Canada
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[e] Chelation Partners Inc, Halifax, NS, Canada
Correspondence:
[*]
Corresponding author. [*]Dr. Christian Lehmann, MD, PhD, FRCPC, Department of Anesthesia, Pain Management and Perioperative Medicine, QE II Health Sciences Centre, 10 West Victoria, 1276 South Park St., Halifax, NS, B3H 2Y9, Canada. Tel.: +1 902 473 2331; Fax: +1 902 423 9454; E-mail: chlehmann@dal.ca.
Note: [1] First and second author contributed equally to the manuscript.
Abstract: BACKGROUND/OBJECTIVE:Non-infectious uveitis is an inflammatory disease of the eye commonly treated by corticosteroids, though important side effects may result. A main mediator of inflammation are oxygen free radicals generated in iron-dependent pathways. As such, we investigated the efficacy of a novel iron chelator, DIBI, as an anti-inflammatory agent in local and systemic models of endotoxin induced uveitis (EIU). METHODS:Firstly, the effects of DIBI in systemic EIU in Lewis rats were established. 2 hours post intravenous LPS or LPS/DIBI injections, leukocyte activation and functional capillary density (FCD) were examined using intravital microscopy (IVM) of the iridial microcirculation. Secondly, the toxicity of DIBI was evaluated in BALB/C mice for both acute and chronic dosages through gross ocular examination, intraocular pressure measurements and hematoxylin-eosin staining of ocular tissue. Lastly, three groups of BALB/C mice, control, LPS or DIBI + LPS, were studied to evaluate the effectiveness of DIBI in treating local EIU. Five hours post-local intravitreal (i.v) injection, leukocyte activation and capillary density were examined via IVM. RESULTS:Treatment of systemic EIU with DIBI resulted in a reduction of leukocyte activation and FCD improvement within the iridial microcirculation. Toxicity studies suggested that acute and chronic DIBI administration had no adverse effects in the eye. In the local EIU model, DIBI was shown to reduce leukocyte activation and restored the FCD/DCD ratio, providing evidence for its anti-inflammatory properties. CONCLUSIONS:Our study has provided evidence that DIBI has anti-inflammatory effects in experimental uveitis. Additionally, no local ocular toxicity was observed.
Keywords: Iron chelation, ocular inflammation, endotoxin, intravital microscopy, microcirculation
DOI: 10.3233/CH-189109
Journal: Clinical Hemorheology and Microcirculation, vol. 69, no. 1-2, pp. 153-164, 2018
