Melatonin Improves Oxidative Stress Injury in Retinopathy of Prematurity by Targeting miR-23a-3p/Nrf2

Abstract

Purpose

Melatonin has promising protective effects for retinopathy. However, its roles in retinopathy of prematurity (ROP) and the underlying mechanisms remain unknown. We aimed to explore its roles and mechanisms in a ROP model.

Methods

Hematoxylin and eosin staining were used to observe the morphology of the retina. Immunofluorescence was used to detect positive (Nrf2+ and VEGF+) cells. Immunohistochemistry was used to detect the level of nuclear expression of PCNA in retinal tissue. Transmission electron microscope (TEM) was used to observe the morphology and structure of pigment cells. qRT-PCR was used to assay the expression of miR-23a-3p, Nrf2, and HO-1. Western blotting was used to detect the expression of Nrf2, HO-1, β-actin, and Lamin B1.

Results

Melatonin or miR-23a-3p antagomir treatment could ameliorate the Oxygen-induced pathological changes, increased the expression of Nrf2 and HO-1, SOD, and GSH-Px, and decreased the expression of VEGF, miR-23a-3p, MDA and the apoptosis in the ROP model. Further target prediction and luciferase reporter assays confirmed the targeted binding relationship between miR-23a-3p and Nrf2.

Conclusion

Our study showed that melatonin could ameliorate H₂O₂-induced apoptosis and oxidative stress injury in RGC cells by mediating miR-23a-3p/Nrf2 signaling pathway, thereby improving retinal degeneration.

Keywords:

• Retinopathy of prematurity
• melatonin
• oxidative stress
• angiogenesis
• miR-23a-3p/Nrf2 pathway

Authors’ contributions

LQL, ZXG, YZ and YF conducted the study design; LQL and ZXG provided Funding; ZXG, YZ and YF carried out experiments and data analysis; YF, XMN and FT supported the technical, and material; ZXG, YZ and YF wrote the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate

This study was approved by the Animal Ethics Committee of Chengdu Medical College (No: CHENGYIDONGLUN2021007).

Disclosure statement

The authors declare that they have no competing interests.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by the Foundation of Sichuan Province Medical Association [grant number S18081]; Foundation of Chengdu Medical College [grant numbers CYZYB20-05]; Foundation of The First Affiliated Hospital of Chengdu Medical College [grant numbers CYFY2020YB04].