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M.R. Fischette, C.–C. Chan, D. Shen, S.P. Mahesh, J. Hochman; TITLE: Antibodies Against LFA–1 Augment Intraocular to Orbital Infiltration of Malignant Lymphoma in a Mouse Model . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4250.
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© ARVO (1962-2015); The Authors (2016-present)
Background: Rev–2–T–6 cells are a T–cell lymphoma of murine origin. Intraperitoneal inoculation of these cells into syngeneic young mice results in brain infiltration followed by migration along the optic nerve sheath into the eye. Intraocular (I.O.) inoculation of Rev–2–T–6 to mature mice results in a disease that closely mimics human PIOL with regards to clinical manifestations as well as cytokine expression patterns. Purpose: To study whether I.O. inoculation of Rev–2–T–6 cells is followed by retrograde migration to the brain and/or systemic infiltration, and to what extent does the introduction of antibody to LFA–1 affect such processes (as this integrin is expressed on Rev–2–T–6 cells and plays a significant role in lymphoma extravasation.) Methods: Two independent experiments were performed. Forty adult Balb/C mice were injected intravitreously, each with105 Rev–2–T–6 cells, and divided into two groups: 1) 20 mice were then injected intraperitoneally, daily, for 21 days with 0.25 µg of Rat–anti mouse LFA–1 monoclonal antibody (in 0.13ml). 2) 20 mice were injected with PBS (0.13ml) for 21 days. These served as controls. Mice were euthanized at various time points based on clinical signs and fundoscopic findings. Histological and immunohistochemical analyses (using an antibody specific to Rev–2–T–6 cells) were used to identify the lymphoma cells in various tissues. Results: Mice in both groups developed intraocular lymphoma. However, none demonstrated lymphoma in the brain, in the contralateral eye, or in any systemic organs. Interestingly, by day 14 post inoculation, 12/20 (60%) mice in the anti–LFA–1 treated group demonstrated marked orbital infiltration of Rev–2–T–6 cells. None of the control group mice (0/20) demonstrated peri–orbital involvement. Conclusions: Treatment with anti–LFA–1 antibodies augments orbital infiltration of Rev–2–T–6 cells from the intraocular compartment (where they are sequestered in the absence of antibody treatment.) This finding suggests that blockage of LFA–1 may result in altering the interactions among the metastasized lymphoma cells and their microenvironment (lymphocyte, macrophage, endothelial cell, etc.) in the eye and orbit.
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