Evidence map›Paper›PMID 40402516›Full record

ArticleInvestigative ophthalmology & visual science2025

Ferroptosis Contributes to Retinal Ganglion Cell Loss in GLAST Knockout Mouse Model of Normal Tension Glaucoma.

Huiwen Ye, Yanlin Feng, Wu Xiang, Zihao Lin, Yue Li, Wen Hu, Keyu Liu, Shuya Tao, Qinmeng Shu, Jiawei Wang and 4 more

Erratum issuedAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Article
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  3. GPX4 promotes optic nerve regeneration and retinal ganglion cell neuroprotection.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
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  4. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Huiwen YeState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Yanlin FengState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Wu XiangState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Zihao LinState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Yue LiDepartment of Ophthalmology, The People's Hospital of Guangxi Zhuang Autonomous Region and Guangxi Key Laboratory of Eye Health and Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology and Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, Guangxi, China.
Wen HuDepartment of Ophthalmology, The People's Hospital of Guangxi Zhuang Autonomous Region and Guangxi Key Laboratory of Eye Health and Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology and Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, Guangxi, China.
Keyu LiuDepartment of Ophthalmology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Shuya TaoState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Qinmeng ShuEye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Key Laboratory of Myopia (Fudan University), Chinese Academy of Medical Sciences, National Health Commission, Shanghai, China.
Jiawei WangDepartment of Ophthalmology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Fan XuDepartment of Ophthalmology, The People's Hospital of Guangxi Zhuang Autonomous Region and Guangxi Key Laboratory of Eye Health and Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology and Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, Guangxi, China.
Yue XuState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Yantao WeiState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Jingjing HuangState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: Visual impairment from normal-tension glaucoma (NTG) poses an increasing burden, yet the underlying mechanism remains unclear. Investigating protective mechanisms for NTG is critical. We aimed to investigate the role of ferroptosis in retinal ganglion cell (RGC) damage in glutamate-aspartate transporter (GLAST) knockout (GLAST-/-) mice, a model for NTG, and also to determine whether inhibiting ferroptosis can provide neuroprotection. Methods: GLAST-/- mice and a glutamate-induced excitotoxicity model in primary RGCs were used to investigate retinal and RGC damage. RNA sequencing identified ferroptosis-related pathways in GLAST-/- retinas. Oxidative stress, lipid peroxidation, and ferroptosis activation were assessed using western blotting and immunofluorescence. Immunohistochemistry (IHC) assessed lipid peroxidation and ferroptosis activation in human retinal tissue. Ferrostatin-1 (Fer-1) was administered to evaluate its neuroprotective effects on RGC survival, retinal thickness, and visual function. Results: RNA sequencing revealed significant enrichment of ferroptosis-related pathways in GLAST-/- retinas. Both GLAST deletion and glutamate-induced excitotoxicity increased oxidative stress, lipid peroxidation, and ferroptosis activation in RGCs. IHC in human retinas confirmed elevated 4-hydroxynonenal (4-HNE) and acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) expression. Furthermore, Fer-1 treatment significantly reduced lipid peroxidation, thereby attenuating the ferroptosis pathways. This intervention ameliorated RGC loss associated with GLAST deletion, protected retinal structure and thickness, and improved amplitudes of the photopic negative response, a-wave, b-wave, and oscillatory potentials. Conclusions: Ferroptosis significantly contributes to RGC and retinal damage in the GLAST-deletion NTG model. Inhibiting ferroptosis with Fer-1 presents a promising therapeutic strategy for protecting visual function in NTG.

Indexed as

Excitatory Amino Acid Transporter 1FerroptosisLow Tension GlaucomaRetinal Ganglion CellsAnimalsBlotting, WesternCyclohexylaminesDisease Models, AnimalElectroretinographyExcitatory Amino Acid Transporter 3HumansIntraocular PressureLipid PeroxidationMaleMiceMice, Inbred C57BLCyclohexylaminesExcitatory Amino Acid Transporter 1Excitatory Amino Acid Transporter 3ferrostatin-1PhenylenediaminesSlc1a1 protein, mouseSlc1a3 protein, mouse

Identifiers

PMID40402516
PMCPMC12110597

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.