Abstract
Purpose :
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.
Methods :
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.
Results :
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).
Conclusions :
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.