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Editors Selection IGR 9-4
Basic research: Retinal oxidative stress
Comment by Rosario Hernandez on:
17008 Mechanisms of immune system activation in glaucoma: oxidative stress-stimulated antigen presentation by the retina and optic nerve head glia, Tezel G; Yang X; Luo C et al., Investigative Ophthalmology and Visual Science, 2007; 48: 705-714
There is suggestive evidence that immune responses may play a role in the pathogenesis of glaucoma patients. Previous work by has established that retinal ganglion cell (RGC) death and axonal loss in glaucoma may occur in response to increased generation of reactive oxygen species (ROS) and subsequent oxidative stress. There are conflicting hypothesis on the role of the immune system in glaucoma, both neuroprotective and neurodestructive roles have been proposed. The study by Tezel et al. (92) proposes that reactive astrocytes and excessive oxidative stress may converge on the activation of the immune response in glaucomatous eyes. The study uses primary cultures of rat retinal glial cells, optic nerve head astrocytes and microglia. T-cell cultures were obtained from rats immunized with basic myelin protein (MBP). ROS were generated in the glial cell cultures using known methods. The effects of ROS on the phenotype of glia cells were determined. The principal findings of these experiments were that exposure to ROS caused increased expression of MHC class II molecules in glial cells, that glial cells are quite resistant to oxidative stress, and that ROS-treated glial cells induced activation of T cells. T cells co-cultured with ROS-treated glial cells synthesized large amounts of TNF-α compared to the secretion from glial cells alone. Treatment with a vitamin E antioxidant abolished T-cell proliferation, MHC class II expression and cytokine secretion in ROS-treated glial cells. This paper is rather complex, however, one can conclude that oxidative stress stimulates antigen-presenting cell properties of astrocytes and microglia. The mechanisms of immunological surveillance in the retina and in the optic nerve head are qualitatively lower that in peripheral tissues that do not have blood brain barrier limiting the access of foreign macromolecules and immune cells. In this paper, ROS induce the expression of the molecular machinery to present antigens in astrocytes and microglia that are necessary for interactions with T cells. Whether reactive astrocytes and microglia acting as professional antigen presenting cells will be able to initiate and amplify specific immune responses in the retina and optic nerve head in vivo remains unclear.
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