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I.D. Subak-Sharpe, K. Watts, G. Wallace, J. Marshall, M.R. Stanford; In vivo Activation of Retinal Antigen Specific T-cells Alters Retinal Wound Healing in a Laser Injury Model . Invest. Ophthalmol. Vis. Sci. 2003;44(13):569.
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Purpose: To determine whether the immuno-pathological features of retinal wound healing following laser-induced injury differ with or without in vivo activation of retinal antigen specific T-cells. Methods: Two groups of 16 PVG rats were used. In group 1, the animals received a controlled laser injury to one eye (Keeler diode laser, 6 discreet applications of 100µm, 100ms, 50mw), without immunisation. In group 2, animals were immunised subcutaneously with bovine retinal extract (containing 1mg/100µl) in complete Freund's adjuvant and intra-peritoneal pertussis toxin. At day 12 following immunisation, before any clinical signs of disease, one eye received the same laser protocol. Retinas were removed at 2 hours and 4, 7 and 28 days following laser injury and examined both histologically and by immunophenotyping (ED1, ED2, ED3, CD4, CD8 staining) of invading cells. T-cell proliferation assays of spleen cells were carried out using retinal extract as the antigen. Results: In group 1, there was an influx of ED1+ve macrophages from day 4 at the sites of laser injury, both within the sub-retinal space and in the localised glial scar. In group 2, a 5x increase of invading ED1 +ve macrophages in the sub-retinal space was observed from day 4, with widespread damage to the rod outer segments. There was also a massive infiltration of macrophages into the vitreous. In the control eyes of group 2, there was no histopathological evidence of inflammatory infiltration in the outer retina or vitreous. Immunisation led to a 3x increased stimulation index for the T-cell proliferation assay. Conclusions: In vivo activation of retinal antigen specific T-cells by immunisation heightens the tissue destructive response following laser injury by enhancing the cellular effector phase of the immune response. These results suggest that caution should be exercised when using laser retinal photocoagulation in patients with uveitis.
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