Emerging role of ferroptosis in diabetic retinopathy: a review

Abstract

Background

Diabetic retinopathy (DR) is a significant complication of diabetes and the primary cause of blindness among working age adults globally. The development of DR is accompanied by oxidative stress, characterised by an overproduction of reactive oxygen species (ROS) and a compromised antioxidant system. Clinical interventions aimed at mitigating oxidative stress through ROS scavenging or elimination are currently available. Nevertheless, these treatments merely provide limited management over the advanced stage of the illness. Ferroptosis is a distinctive form of cell death induced by oxidative stress, which is characterised by irondependent phospholipid peroxidation.

Purpose

This review aims to synthesise recent experimental evidence to examine the involvement of ferroptosis in the pathological processes of DR, as well as to explicate the regulatory pathways governing oxidative stress and ferroptosis in retina.

Methods

We systematically reviewed literature available up to 2023.

Results

This review included 12 studies investigating the involvement of ferroptosis in DR.

Graphical Abstract

Schematic diagram of potential pathways leading to DR caused by ferroptosis. Characteristic manifestations of DR in the retina include haemorrhage, hard exudation, angiogenesis, and neurodegeneration. Iron accumulation, lipid peroxidation, and impaired antioxidant defence systems induced ferroptosis in diabetic retinopathy, resulting in compromised retinal cell viability, disrupted cell-to-cell junctions, and elicited inflammatory responses.

Keywords:

• Diabetic retinopathy
• ferroptosis
• neuroinflammation
• oxidative stress
• lipid peroxidation

Acknowledgements

The figures in this review were created with Adobe Illustrator 2022.

Author contributions

Conceptualisation, X.-X.C. resources, R.-H.W. and S.-Y.R. writing - original draft, R.-H.W. and X.-X.C. writing - review & editing, K.X. and Z.Z. supervision, X.-F.S. funding acquisition, X.-H.C. and X.-F.S. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China under Grant (81974136); Youth fund of National Natural Science Foundation of China under Grant (82000927); Key Research and Development Program of Hubei Province under Grant (2022BCA01); and Natural Science Foundation of Hubei Province under Grant (2020CFB208).