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Rebecca Scholz, Alexander Aslanidis, Marcus Karlstetter, Khalid Rashid, Christian Grimm, Thomas Langmann, ; Targeting the translocator protein (18kDa) (TSPO) prevents microglia reactivity and protects from from light induced retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):430.
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© ARVO (1962-2015); The Authors (2016-present)
Microglia activation is a common hallmark of several retinal degenerative diseases. Our previous work showed that TSPO is a marker for reactive retinal microglia and that the selective TSPO ligand XBD173 exerts strong anti-inflammatory effects on microglia in vitro. In the present study, we investigated whether XBD173 has the capacity to modulate retinal microglia in vivo and thereby protects from light induced retinal degeneration.
BALB/C mice were treated with vehicle or 10 mg/kg XBD173 by intraperitoneal injection prior to exposure to 15.000 lux white light for one hour. Daily XBD173 treatment was continued for four consecutive days. After this time period, retinal flat-mounts and sections were prepared to analyze microglia morphology, localization and reactivity using Iba1 and TSPO protein expression. Optical coherence tomography, morphometric measurements of retinal thickness and TUNEL stainings were used to to determine the extent of retinal degeneration and photoreceptor apoptosis.
In control eyes that were not exposed to light, Iba1 staining revealed that microglia were located in the inner and outer plexiform layers and showed a ramified morphology. Light exposed animals that were sham treated displayed a severe thinning of the photoreceptor layer and prominent photoreceptor apoptosis which was accompanied by the migration of amoeboid microglial cells into the outer nuclear layer and the subretinal space. TSPO staining revealed a strong TSPO expression in these microglia, indicating a highly reactive status. In contrast, light exposed mice that received XBD173 injections showed a well preserved photoreceptor layer and strongly reduced apoptosis. Significantly fewer numbers of amoeboid microglial cells were present in the ONL and subretinal space and nearly all of them displayed a ramified cell shape. Furthermore, these microglia showed much less staining for the activation marker TSPO.
TSPO-specific XBD173 treatment of mice challenged with intense withe light reduced the number of reactive microglia and protected retinal photoreceptors from light induced apoptosis. We conclude that TSPO and its ligands represent promising targets for neuroprotective and anti-inflammatory therapy of retinal degenerative diseases.
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