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Sandra Kuehn, Pia Grotegut, Andreas Smit, Gesa Stute, H Burkhard Dick, Stephanie C Joachim; Important role of microglia in a novel S100B based retina degeneration model. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4500.
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© ARVO (1962-2015); The Authors (2016-present)
S100B is a glial protein and up-regulated in neurological diseases, like glaucoma, multiple sclerosis and Morbus Alzheimer. In a pilot project, the intravitreal injection of S100B triggered a retina degeneration, possibly based on glia response during neuronal damage. Microglia were described as degenerative player, but could they cause the degeneration? To clarify this question, the microglia activity was inhibited via minocycline, an antibiotic tetracycline derivate, in this S100B model.
Starting at day 0, minocycline hydrochloride (Mino) was daily applicated intraperitoneally in Wistar rats in two doses: 25 mg (Mino I) or 13 mg per kg body weight (Mino II). At day 1, S100B (0.4 µg/2 µl) or PBS were injected intravitreally in one eye per rat (n=6-8/group). At day 14, retinal ganglion cells (RGCs, Brn-3a) in an apoptotic state (cleaved caspase 3) and active microglia (ED1, Iba1) were labeled histologically. The 5 groups (native, PBS, S100B, S100B+Mino I, S100B+Mino II) were statistically analyzed (ANOVA, Tukey post-hoc test).
In comparison to the PBS group (52.0±4.7 cells/mm), S100B application reduced the RGC number significantly (30.3±1.7 cells/mm, p=0.02). Mino treatment inhibited the impact of S100B on RGCs (Mino I: 40.4±5.3 cells/mm, p=0.4; Mino II: 40.1±3.2 cells/mm, p=0.4). The apoptotic rate of RGCs increased through S100B (31.5±3.5%, p<0.001), while both Mino groups (Mino I: 16.7±5.0%, p=0.4; Mino II: 8.0±1.7%, p>0.9) showed comparable values to the PBS group (7.3±3.9%). Furthermore, higher counts of active microglia were detected in the S100B group (5.2±0.5 cells/mm, p<0.001) compared to the PBS group (2.4±0.4 cells/mm). Microglia counts of the Mino groups were similar to the PBS group (Mino I: 2.9±0.2 cells/mm, p=0.8; Mino II: 2.5±0.4 cells/mm, p<0.9).
At day 14, first signs of degeneration were noted for this novel retina degeneration model which is based on the intraocular injection of S100B. Apoptotic mechanisms and a microglia response were still in process, while RGCs were already damaged. This damage seems to be mainly based on microglia response, since apoptotic processes and microglia activity were down-regulated through minocycline. This led to a rescue of some RGCs. Further evaluations of this new model are important to get more information about the pathomechanisms of S100B and glia cells during glaucoma.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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