Neuroprotective Effect of Brazilian Green Propolis on Retinal Ganglion Cells in Ischemic Mouse Retina

ABSTRACT

Purpose

The current study was undertaken to investigate whether Brazilian green propolis (BGP) can increase the viability of retinal ganglion cells (RGCs) in ischemic mouse retina, and examined the possible mechanisms underlying this neuroprotection.

Materials and Methods

C57BL/6J mice were subjected to constant elevation of intraocular pressure for 60 min to establish retinal ischemia-reperfusion injury. Mice then received saline or BGP (200 mg/kg) intraperitoneally once daily until sacrifice. The expression of hypoxia-inducing factor (HIF)-1α and glial fibrillary acidic protein (GFAP) and the level of histone acetylation were assessed at 1, 3, and 7 days after injury. The expression of Bax, Bcl-2, p53, NF-κB, Nrf2, and HO-1 were also analyzed at 3 days after injury. The neuroprotective effect of BGP treatment on RGC survival was evaluated using Brn3a immunohistochemical staining.

Results

The expression of HIF-1α and GFAP was increased and the level of histone acetylation decreased in saline-treated ischemic retinas within 7 days. BGP treatment effectively attenuated the elevated expression of HIF-1α, GFAP, Bax, NF-κB and p53. The expression of Bcl-2, Nrf2, HO-1 and the level of histone acetylation increased by BGP treatment, resulting in a significant difference between BGP-treated and saline-treated retinas. Immunohistochemical staining for Brn3a also revealed that BGP treatment protected against RGC loss in ischemic retina.

Conclusions

Our results suggest that BGP has a neuroprotective effect on RGCs through the upregulation of histone acetylation, downregulation of apoptotic stimuli, and suppression of NF-κB mediated inflammatory pathway in ischemic retina. These findings suggest that BGP is a potential neuroprotective agent against RGC loss under oxidative stress.

KEYWORDS:

• Ischemia
• Propolis
• Neuroprotection
• Retinal ganglion cell
• Histone acetylation

Acknowledgments

This research was supported by the Basic Science Research Program through the NRF of Korea funded by the Ministry of Education (NRF-2015R1D1A1A01059630) and by the grant Chonnam National University Hospital Biomedical Research Institute (BCRI18019 and BCRI18025). The funding organizations had no role in the design or conduct of this research.

Conflicts of Interest

The authors indicated no potential conflicts of interest.

Additional information

Funding

This work was supported by the National Research Foundation of Korea [NRF-2015R1D1A1A01059630]; Chonnam National University Hospital Biomedical Research Institute [BCRI18019 and BCRI18025].