Improved Retinal Ganglion Cell Survival through Retinal Microglia Suppression by a Chinese Herb Extract, Triptolide, in the DBA/2J Mouse Model of Glaucoma

Abstract

To investigate the changes in retinal microglia and retinal ganglion cell (RGC) survival after long-term administration of a Chinese herb extract, triptolide, in a DBA/2J mice. DBA/2J mice (n = 96) were administered triptolide (n = 48) 25 µg/kg or vehicle (n = 48) and were judged at 7, 9, 11 months of age. Long-term triptolide treatment tended to attenuate the anterior segment pathology in experimental group, though intraocular pressure was not significantly different between the two groups. In the experimental group, RGC survival was improved (7, 9, 11 months: p = 0.035, 0.004, 0.014), and microglia activation was suppressed based on a more ramified appearance (9, 11 months: p = 0.024, 0.013) and a lower total microglial cell count (7, 9, 11 months: p = 0.028, 0.025, 0.014). Double-immunofluorescence staining revealed TNF? localized to microglia, TNFR1 localized to the RGCs and nerve fiber layer. These findings indicate that long-term triptolide administration suppressed microglia activation and improved RGC survival in DBA/2J mice.

Tetrandrine Suppresses Lipopolysaccharide-Induced Microglial Activation by Inhibiting NF-κB and ERK Signaling Pathways in BV2 Cells

“…The progressive degeneration of retinal ganglion cells (RGCs) and sustained loss of the visual field are its remarkable characteristics [12]. Recent studies suggested that activated microglia participate in the pathological course of glaucomatous optic injury with adverse consequences [13], [14], and reduced microglial activation was associated with alleviating optic nerve and retinal neurodegeneration [15].…”

Time course of bilateral microglial activation in a mouse model of laser-induced glaucoma

“…the OS, OPL, IPL, and GCL-NFL. Most studies of microglial activation over time after OHT have involved a DBA/2 J mouse model of inherited glaucoma [34][35][36][37][38] . Other studies have relied on rat glaucoma models, in which OHT is induced differently than in our model 21,[39][40][41][42][43][44][45] .…”

Molecular Targets Involved in the Neuroprotection Mediated by Terpenoids

“…Protective effects of triptolide on dopaminergic neurons damage were mediated by the inhibition of proinflammatory mediators from activated microglia, as demonstrated in MPP+-induced hemiparkinsonian rats [67], with an improvement in behavioral disabilities. Additionally, preclinical glaucoma studies have demonstrated that this diterpenoid improved RGC survival through the suppression of microglia activation and proliferation in glaucoma rat models [68,69]. Besides having protective effects via the microglia, triptolide exhibited in vitro neurotrophic activity via stimulation of the production and release of NGF in astrocytes [70].…”