Abstract
Asiatic acid (AA), a pentacyclic triterpene derived from the tropical medicinal plant Centella asiatica, has been widely used as an antioxidant and anti-inflammatory agent. Evidence regarding the neuroprotective properties of AA is emerging. However, the protective effects of AA and its mechanism in glaucoma are poorly understood. In the current study, we investigate the neuroprotective effect and mechanism of AA on retinal ganglion cells (RGCs) in a rat model of glaucoma. Elevated intraocular pressure (IOP) was induced in adult rats by injecting microspheres into the anterior chamber. AA was intravitreally injected into glaucomatous rats. RGC densities were analyzed by evaluating surviving RGC number of the retinal flatmounts and retinal sections, and the apoptotic cell number were evaluated by analyzing retinal sections. RGC function was assessed by measuring the photopic negative response (PhNR). Retinal Bcl-2, Bax, and cleaved caspase-3 expression were determined using a Simple Western System, real-time PCR and immunofluorescence staining. AA reduced the loss of RGCs and decreased the apoptotic RGC number. AA exerted neuroprotective effects and ameliorated retinal dysfunction in impaired RGCs in a rat model of glaucoma. AA protected RGCs by upregulating the expression of the antiapoptotic protein Bcl-2 and downregulating the expression of the pro-apoptotic proteins Bax and caspase-3. This study has provided important evidence indicating that AA may be a potential therapeutic agent for glaucoma.
Highlights
Glaucoma is a leading cause of irreversible vision loss and is characterized by the progressive loss of retinal ganglion cells (RGCs) and their axons (Jonas et al, 2017)
We investigated the neuroprotective effects of Asiatic acid (AA) on RGC apoptosis and function and further explored the underlying mechanisms
The intraocular pressure (IOP) was significantly elevated (Chan et al, 2007) on the third day after the microbead injection (27.27 ± 5.86 mmHg in the chronic ocular hypertension (COHT) group compared with 10.80 ± 1.47 mmHg in the normal control (NC) group, n = 24, p < 0.001)
Summary
Glaucoma is a leading cause of irreversible vision loss and is characterized by the progressive loss of retinal ganglion cells (RGCs) and their axons (Jonas et al, 2017). AA decreases intracellular free radical concentrations to prevent H2O2-induced cell death (Jew et al, 2000) and rescues primary rat cortical cells from glutamate-induced toxicity (Lee et al, 2000). AA has been reported to exert neuroprotective effects on focal cerebral ischemia and embolic stroke in vivo by preserving the blood–brain barrier (BBB) integrity, reducing the infarct sizes and attenuating mitochondrial damage (Krishnamurthy et al, 2009; Lee et al, 2012, 2014; Tabassum et al, 2013). Because AA shows numerous mechanisms that may exert beneficial effects on neurodegenerative diseases, we hypothesized that AA may promote RGC survival in a rat model of glaucoma. We investigated the neuroprotective effects of AA on RGC apoptosis and function and further explored the underlying mechanisms
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