Abstract
Purpose::
Growing evidence supports immune system involvement in glaucomatous neurodegeneration. In addition to the evidence of an aberrant activation of the immune system in glaucoma patients, oxidative stress evident in the ocular hypertensive retina and optic nerve head has been associated with the activation of glial antigen presentation and stimulation of T cells during glaucomatous neurodegeneration. This study aimed to determine T cell response in a chronic pressure-induced rat model of glaucoma.
Methods::
Intraocular pressure elevation was induced in rats by hypertonic saline injections into episcleral veins. Following an ocular hypertensive period of up to 12 weeks, immunohistochemistry was performed to determine MHC class II molecules on resident immune-regulatory glial cells. T cells were isolated from regional lymph nodes of ocular hypertensive and normotensive animals. To determine T cell response to retinal proteins, T cell proliferation was determined by [3H]-thymidine incorporation and cytokine secretion wasmeasured using enzyme-linked immunosorbent assay.
Results::
Glial MHC class II expression was up-regulated in the retina and optic nerve head of ocular hypertensive eyes, predominantly including microglial cells with an over four-fold increase in quantitative grading of immunolabeling. In addition, T cells isolated from ocular hypertensive animals exhibited an approximately three-fold stimulated response to retinal proteins compared with controls. Increased reactivity of T cells to retinal proteins in ocular hypertensive animals was correlated with cumulative intraocular pressure exposure and neuronal damage.
Conclusions::
Findings of this in vivo study reveal that a stimulated T cell response accompanies glaucomatous neurodegeneration in ocular hypertensive eyes, and support that secondary to ocular hypertension, tissue stress and/or injury, an immunogenic component may eventually be involved in the neurodegenerative process. In addition to other factors evident in glaucomatous tissues (increased antigenicity, increased protein exposure due to tissue injury, and increased co-stimulatory factors such as reactive oxygen species), increased antigen presenting ability of glial cells also appears to be associated with the activation of a systemic immune response during glaucomatous neurodegeneration.
Keywords: neuroprotection • glia • immunomodulation/immunoregulation