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R. Iezzi, A. Kennedy, I. Glybina, G. Abrams; Fluocinolone Acetonide-Mediated Microglia Suppression in RCS Rat Model of Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3719.
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© ARVO (1962-2015); The Authors (2016-present)
We have previously shown that Fluocinolone Acetonide (FA), a synthetic steroid, is neuro-protective in the RCS rat model of retinal degeneration. The purpose of this study was to assess the role of FA-mediated microglial cell suppression in photoreceptor neuroprotection.
Four groups of RCS rats (5 weeks old, 3 rats per group) were randomly assigned and implanted with intra-ocular, sustained-release FA devices as follows, 1.) 0.5 µg/day FA; 2.) 0.2 µg/day FA; 3.) inactive implant; 4.) untreated control. Electroretinograms (ERGs) were recorded pre-implantation and weekly, post-op. Rats were sacrificed at 9-weeks of age. The eyes were enucleated and retinas prepared as whole flat mounts or in transverse section and stained with antibodies against the microglial markers Iba-1, ED-1 and the macrophage marker, ED-2. Sections and whole mounts were examined by fluorescence microscopy and stained cells counted in standardized fields from all groups. Data were analyzed using one-way ANOVA, followed by multiple pairwise comparisons via the Tukey test.
In retinal whole mounts and sections, microglial cells were identified in four distinct layers by Iba-1 staining, corresponding to an inner layer (IL), adjacent to the retinal ganglion cells, a middle layer (ML), a layer at the photoreceptors (PL) and a layer within the outer-debris zone (DL). Mean IL, PL and DL microglial cell counts were significantly lower in FA-treated eyes as compared to placebo controls (p<0.002). Treated eyes of both FA groups demonstrated 43% fewer PL microglia on IBA-1 sections. Microglial cells in FA-treated groups also had a more "tuberous" morphology compared to the amoeboid characteristics of activated cells. In transverse sections labelled with ED-1 antibody for activated microglia, staining was seen within the DL, only. FA-treated groups demonstrated an 87% reduction in the number of activated DL- microglial cells (p=0.001). All retinal preparations were uniformly negative for ED-2, indicating that staining was not due to infiltration of blood-borne macrophages into the retina.
FA has profound effects on retinal microglia. FA reduced overall microglial cell counts as well as the number of activated microglia. In addition, FA-treated microglia assumed an inactive morphology. Anti-inflammatory Microglial Suppression Therapy (MST) may provide an approach to the treatment of patients with retinal neurodegenerative diseases such as Retinitis Pigmentosa and Age-Related Macular Degeneration.
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