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Elisabeth Rungger–Brändle, André A. Dosso, Peter M. Leuenberger; Glial Reactivity, an Early Feature of Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2000;41(7):1971-1980.
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purpose. To characterize early structural gliotic reactions in retinal
Müller cells, astrocytes, and microglia in experimentally induced
methods. Rats were rendered diabetic by streptozotocin injection and killed
after 2, 4, 12, or 20 weeks. Cell densities were determined in
flatmounted retinas or transverse semithin sections. Expression of
glial fibrillary acidic protein (GFAP) was localized on frozen sections
or flatmounts by immunofluorescence and confocal microscopy, and GFAP
content was evaluated by Western blot analysis. Microglial cells were
visualized by binding of isolectin B4 or staining with antibodies to
phosphotyrosine residues. The integrity of the blood–retinal barrier
was assessed by intravenous injection of Evans blue.
results. The density of Müller cells and microglia was significantly
increased at 4 weeks of diabetes compared with nondiabetic controls.
GFAP expression in Müller cells was not detected at 4 weeks but
was prominent at 12 weeks. The number of astrocytes was significantly
reduced at 4 weeks in the peripapillary and far peripheral retina.
Shape changes of microglial cells indicated functional activation.
Leakage of the blood–retinal barrier was observed at 2 weeks of
hyperglycemia, the earliest time point investigated.
conclusions. The leakage of the blood–retinal barrier before glial reactivity
suggests that glia are early targets of vascular hyperpermeability. The
individual glial cell types react differentially to the diabetic state.
Müller cells undergo hyperplasia preceding GFAP expression, and
microglial cells are activated, whereas astrocytes regress. This glial
behavior may contribute decisively to the onset and development of
neuropathy in the diabetic retina.
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