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Andreas Smit, Pia Grotegut, Sandra Kuehn, Gesa Stute, Burkhard Dick, Stephanie C Joachim; Minocycline protects retinal ganglion cells and optic nerve structure in an immune mediated retina degeneration model. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3111.
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© ARVO (1962-2015); The Authors (2016-present)
Previous studies have shown that intraocular injection of S100B leads to glaucoma-like damage in a rodent model (Kuehn et al., 2018). Also, a microglial response was found in this model. The role of this microglial reaction in the degenerative processes remains unclear. Hence, we inhibited the microglial activity by systemic minocycline treatment.
Four groups were part of the study. Three groups received intraocular S100B injections whereas PBS served as a control. Two groups amongst the S100B groups received additional intraperitoneal injections of minocycline hydrochloride in two different doses (25 mg/kg BW=mino I and 13.5 mg/kg BW=mino II). Minocycline treatment started one day prior to intraocular injections and was continued daily for 14 days. At day 14 immunohistochemical analysis of retinal ganglion cells (Brn-3a) as well as apoptosis (cleaved caspase 3) followed. Additionally, the neurofilament (SMI-32) and microglia (Iba1/ED1) of the optic nerve (ON) were analyzed.
A decrease in retinal ganglion cell (RGC) numbers was noted in the S100B group (30.3±1,7 cells/mm, p=0.02) compared to the PBS group (52.0±4.7 cells/mm). Also, an increase of apoptotic activity was observed in the S100B group (31.5±3.5%, p<0.001) in comparison to the control (7.3±3.9%). Minocycline groups showed apoptotic activity similar to the control group (mino I: 16.7±5.0%, p=0.4; mino II: 8.0±1.7%, p>0.9), as well as a tendency to RGC protection (mino I: 40.4±5.3 cells/mm, p=0.4; mino II: 40.1±3.2 cells/mm, p=0.4). S100B injection lead to an increase of optic nerve neurofilament score (1.3±0.1, p=0.016) indicating loss of structural integrity compared to control group (0.8±0.1). In minocycline treated groups, a dose-dependent protection of the nerve structure occurred (mino I: 1.1±0.2, p=0.448; mino II: 0.9±0.3, p<0.05). Furthermore, a significant increase in microglial cell count has been shown in the S100B group (167.9±22.9%, p<0.001) compared to the control (108.3±16.4%) that could not be seen in the minocycline groups (mino I: 95.4±15.1%, p=0.68; mino II=100.4±10.3%, p=0.9).
An inhibition of the microglial response through minocycline has a protective effect on the retinal and optic nerve structure. However, the damage has not been prevented completely, thus the microglial response only seems to have a partial role in the degenerative process.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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