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Edward H. Hughes, Frank C. Schlichtenbrede, Conor C. Murphy, Gian-Marco Sarra, Philip J. Luthert, Robin R. Ali, Andrew D. Dick; Generation of Activated Sialoadhesin-Positive Microglia during Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2003;44(5):2229-2234. doi: 10.1167/iovs.02-0824.
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purpose. The retina contains a rich network of myeloid-derived cells (microglia) within the retinal parenchyma and surrounding vessels. Their response and behavior during inflammation and neurodegeneration remain largely undefined. In the present study, the behavior of microglia was closely examined during the onset of photoreceptor degeneration in the rds mouse, to assess their role in photoreceptor apoptosis. The results may have relevance to similar degeneration in humans (retinitis pigmentosa).
methods. Retinas from rds and wild-type CBA mice aged 8, 14, 16, 17, 19, 21, 30, and 40 days were examined immunohistochemically, with antibodies to macrophage cell surface markers, inducible nitric oxide synthase (iNOS), and proliferating cell nuclear antigen (PCNA), during the most active phase of the disease. TUNEL was used to assess photoreceptor apoptosis.
results. In the rds mouse, microglia proliferated in situ (PCNA), migrated to the subretinal space, and adopted an activated phenotype. Maximum microglial cells occurred at postnatal day (P)21, 5 days after the peak in photoreceptor apoptosis (P16). Microglia did not express iNOS, and nitrotyrosine was absent. Sialoadhesin was expressed on microglia from P14, and expression was greatest at P21.
conclusions. During retinal degeneration, microglia are activated and express sialoadhesin. The temporal relationship between photoreceptor apoptosis and microglial response suggests that microglia are not responsible for the initial wave of photoreceptor death, and this is corroborated by the absence of iNOS and nitrotyrosine. Expression of sialoadhesin may indicate blood-retinal barrier breakdown, which has immune implications for subretinal gene therapeutic strategies.
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