Purchase this article with an account.
Li PAN, Kin-Sang Cho, Dongfeng Chen, Chi-wai Do; Baicalein Alleviates Microglia-mediated Neuroinflammation and Neurodegeneration in Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1486.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Excessive microglia activation is considered as a pathological factor that leads to neuroinflammation and neurodegeneration. Baicalein (Ba), a natural occurring flavonoid, displays a wide spectrum of bioactivities including anti-inflammation. In this study, we investigated the effects of Ba on the lipopolysaccharide (LPS)-induced microglia activation in mouse BV2 microglia cell line. We also evaluated the anti-inflammatory and neuroprotective effects of Ba using a retinal ischemia/reperfusion (I/R) mouse model.
Activation of BV2 cells was induced by 1μg/ml LPS for 6 hours prior to the addition of PBS, vehicle or Ba (10μM). After a total 48-hour incubation, pro-inflammatory cytokine protein and mRNA levels were quantified by cytokine array assays and quantitative polymerase chain reaction (qPCR), respectively. For in vivo studies involving I/R injury, the morphological and transcriptome changes of mouse microglia and retinas were evaluated, either in the presence or absence of Ba (100μM) treatment.
As expected, upregulation of pro-inflammatory cytokines was detected in LPS-primed BV2 cells. Ba effectively suppressed the expression of most cytokines including IL-6, IL-1β, and TNF-α, as compared to the vehicle-treated group which showed a similar expression profile as LPS-stimulated control. Concurrently, Ba significantly suppressed the mRNA expression of Il-6, Il-1β and Tnf-α in LPS-stimulated BV2 cells. After 1 week of I/R injury, mouse retinas displayed an increased population of IBA-1+ microglia/macrophages along with enlarged IBA-1+ cell body and shortened cellular processes, as well as an increased expression of activated microglia markers (e.g. Iba-1, Cox2) and pro-inflammatory cytokines (e.g. Il-1β, Il-1α). Weekly intravitreal administration of Ba retained the morphological and transcriptional features of resting microglia. Ba also effectively reduced the retinal ganglion cells (RGCs) loss by 80% at 4 weeks after I/R injury.
Our results suggest that Ba acts as a negative regulator of activated microglia and immune responses both in vitro and in vivo, effectively alleviating neurodegeneration in retinal I/R injury. This finding indicates that Ba could be a potential therapeutic agent to neurodegenerative retinal diseases.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
This PDF is available to Subscribers Only