Hesperidin Exherts Antiglaucoma Effects by Activating Overexpression of BMP4 Signaling and Management of Retinal Ganglionic Cells Degeneration

Abstract

We investigated the effect of hesperidin on bone morphogenetic protein 4 signaling, which is involved in preventing retinal ganglion cell degeneration in rats with glaucoma. We investigated the therapeutic efficacy of hesperidin as an enhancer of the bone morphogenetic protein 4 signaling pathway at three dose levels (50, 100, and 200 mg/kg) using a rat glaucoma model produced by injecting conjunctival fibroblasts intracamerally into the eyes of the animals. Bone morphogenetic protein 4 was stimulated with bilateral intravitreal injections of 2 mL adeno-associated virus vectors cloned with bone morphogenetic protein 4 primers into the right eye. The intraocular pressure, expression of bone morphogenetic protein 4 and Smad 4, and the distribution of the retinal ganglion cells count were performed a week following the onset of glaucoma. When compared to the model group, the retinal ganglion cells survival rate was increased proportionately in the hesperidin group (P < 0.01). A significant increase in bone morphogenetic protein 4 messenger ribonucleic acid expression was observed in the hesperidin group (P < 0.01) compared to the model group. The hesperidin group showed similar positive results (P < 0.01) with intraocular pressure, Western blot analysis, retinal explant culture, and histological analysis. Further, the model group showed a decline in retinal ganglion cells survival rate (P < 0.01) compared to the control group, and similar trends were noticed in intraocular pressure, Western blot analyses, retinal explant culture, and histological analysis. According to our findings, hesperidin increases the activity of the bone morphogenetic protein 4 pathway, which in turn increases the survival of retinal ganglion cells and the function of the eyes in an experimental glaucoma model.