Murine Model of Primary Intraocular Lymphoma

Purpose: Primary intraocular lymphoma (PIOL) is a subtype of central nervous system lymphoma. Although this lymphoma is rare, its incidence has tripled in the past 15 years. Currently, the only available model is a murine metastatic malignant lymphoma that occurs after intraperitoneal inoculation of Rev-2-T-6 lymphoma cells into newborn syngeneic mice. The current study was conducted to develop a new experimental model for PIOL.

Methods: Rev-2-T-6 cells (0.5 x 10(5) or 1.0 x 10(5)) were inoculated into the vitreous of adult BALB/c mice. Mice were monitored clinically every other day and under fundoscopic examination weekly. They were euthanatized on weeks 3, 5, 6, 7, or 8, after inoculation. All eyes were processed for histology. Immunohistochemistry was performed with an antibody (p14) specific for Rev-2-T-6 cells. Cytokine mRNA expression (IL-2, -4, -6, -10, and IFN-gamma and CC chemokine receptor-1 [CCR1]) was assayed in the lymphoma cells by microdissection and RT-PCR. IL-10 and -6 levels in the vitreous were measured by ELISA.

Results: Within 2 to 4 weeks, tumor cells from the vitreous migrate through the retina and gather between the RPE cell and retina. Rarely (>2 months after inoculation), Rev-2-T-6 cells may break through the RPE and infiltrate the choroid and sclera. Tumor localization was confirmed by immunohistochemistry. The intraocular lymphoma cells produce high levels of IL-10, IFN-gamma, and CCR1 transcripts. A high level of IL-10 was detected in the vitreous inoculated with Rev-2-T-6 cells.

Conclusions: The data suggest that RPE cells constitute a barrier to the spread of intraocular lymphoma. Intravitreal injection of Rev-2-T-6 cells is a novel model of PIOL in immune-competent hosts that will aid in understanding the molecular mechanisms of the disease.