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Published on: January 12, 2024
Targeting Novel Regulated Cell Death: Pyroptosis, Necroptosis, and Ferroptosis in Diabetic Retinopathy
Sheng Gao1,2, Yun Zhang1,2, Meixia Zhang1,2
1Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China.
Abstract:
Diabetic retinopathy (DR) is one of the primary causes of visual impairment in the working-age population. Retinal cell death is recognized as a prominent feature in the pathological changes of DR. Several types of cell death occurrence have been confirmed in DR, which might be the underlying mechanisms of retinal cell loss. Regulated cell death (RCD) originates from too intense or prolonged perturbations of the intracellular or extracellular microenvironment for adaptative responses to cope with stress and restore cellular homeostasis. Pyroptosis, necroptosis, and ferroptosis represent the novel discovered RCD forms, which contribute to retinal cell death in the pathogenesis of DR. This evidence provides new therapeutic targets for DR. In this review, we summarize the mechanisms of three types of RCD and analyse recent advances on the association between novel RCD and DR, aiming to provide new insights into the underlying pathogenic mechanisms and propose a potential new strategy for DR therapy.
Insights
Diabetic retinopathy (DR) involves retinal cell death. Novel regulated cell death (RCD) forms like pyroptosis, necroptosis, and ferroptosis offer new therapeutic targets for vision impairment.
Area of Science:
- Ophthalmology
- Cell Biology
- Pathology
Background:
- Diabetic retinopathy (DR) is a leading cause of vision loss in the working-age population.
- Retinal cell death is a key pathological feature in DR, driven by various cell death mechanisms.
- Regulated cell death (RCD) encompasses programmed cell death pathways activated by cellular stress.
Purpose of the Study:
- To review the mechanisms of pyroptosis, necroptosis, and ferroptosis.
- To analyze the association between these novel RCDs and the pathogenesis of DR.
- To explore RCD as a potential therapeutic strategy for DR.
Main Methods:
- Literature review of studies on RCD and DR.
- Summary of molecular mechanisms underlying pyroptosis, necroptosis, and ferroptosis.
- Analysis of experimental evidence linking RCD to retinal cell loss in DR.
Main Results:
- Pyroptosis, necroptosis, and ferroptosis are identified as significant contributors to retinal cell death in DR.
- These RCD pathways are implicated in the progression of DR pathology.
- Understanding these mechanisms provides insights into DR pathogenesis.
Conclusions:
- Novel RCD pathways are crucial in DR-associated retinal cell death.
- Targeting pyroptosis, necroptosis, and ferroptosis presents a promising therapeutic avenue for DR.
- Further research into RCD mechanisms could lead to effective DR treatments.
