Microglial cell activation following retinal detachment: a comparison between species.

Microglial cells are the resident macrophages of the central nervous system (CNS) although they are neither a true glial cell nor a macrophage. They are derived from bone marrow precursor cells that enter the CNS early in development and generally lie “dormant” in adult tissue unless activated in response to various pathological changes including infectious diseases, trauma, inflammation, ischemia, and neurodegeneration [1]. Activated microglia become scavenger cells, phagocytosing cellular debris and killing invading microorganisms. The rapidity of their activation may be in part due to their responsiveness to subtle changes in the microenvironment such as imbalances in ion homeostasis [2] and signaling molecules such as ATP [3,4], acetylcholine and noradrenaline [5], all of which precede structural changes in surrounding cells. Thus, in their “resting” state, microglia seem to monitor their surroundings and remain poised to react quickly to physiological insult. In the retina, microglia become activated in various forms of retinal injury or disease including light damage [6,7], glaucoma [8,9], laser photocoagulation [10], intraocular surgery [11], and the inherited degeneration of the RCS rat [12,13], human retinitis pigmentosa, and age related macular degeneration [14,15]. It is generally presumed that activation of microglia benefits surviving cells by removing debris that may be toxic. However, recent evidence suggests that activated microglia may be detrimental to CNS neuron survival. Indeed, it has been shown that inhibiting microglia activation slows photoreceptor degeneration in the RCS rat [16] and media taken from microglial cell cultures kills photoreceptors [17]. Microglia are known to secrete molecules such as pro-inflammatory cytokines, proteases, tumor necrosis factor, and nitric oxide, all of which can kill neurons [18-20]. For this reason, microglia inhibiting factors are being explored in the treatment of various diseases in the CNS including multiple sclerosis, stroke, Alzheimer’s, and Parkinson’s diseases. The lectin Griffonia simplicifolia labels both microglia and macrophages in the retina of several different species [21], but it does not label cells in human retinal tissue. The lectin Ricinus communis agglutinin I has been used to label microglia and macrophages in human retinal samples [15]. The antibody to CD11b labels a cell surface antigen expressed by granulocytes, monocytes, and macrophages. In some species this antibody also labels microglia within the neural retina [2224], but this is not the case in our preparations of feline retina. Retinal detachment, or the separation of the neural retina from the retinal pigment epithelium (RPE), can occur as a result of varied conditions including trauma, inflammatory eye disease, or the presence of retinal holes or tears. In all cases, detachment initiates a cascade of events beginning in photoreceptors with outer segment degeneration [25-27] and fol©2005 Molecular Vision