Evidence mapPaperPMID 41649692Full record

ArticleMolecular neurobiology2026

ACSL4 Inhibition by AS-252424 Protects Visual Function by Suppressing RGC Ferroptosis After Retinal Ischemia Reperfusion Injury.

Keyu Liu, Zihao Lin, Wu Xiang, Jiayi Zhang, Xiaofeng Wu, Chenzhao Ma, Yantao Wei, Jiawei Wang, Jianqiao Li

Abstract read
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In one paragraph

Article in Molecular neurobiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Keyu Liu *Department of Ophthalmology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, #107 Wenhuaxi Road, Jinan, 250014, China.
Zihao Lin *Zhongshan Ophthalmic Center, Sun Yat-Sen University, WHO Collaborating Centre for Eye Care and Vision, State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, #7 Jinsui Road, Guangzhou, 510060, China.
Wu Xiang *Zhongshan Ophthalmic Center, Sun Yat-Sen University, WHO Collaborating Centre for Eye Care and Vision, State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, #7 Jinsui Road, Guangzhou, 510060, China.
Jiayi ZhangDepartment of Ophthalmology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, #107 Wenhuaxi Road, Jinan, 250014, China.
Xiaofeng WuDepartment of Ophthalmology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, #107 Wenhuaxi Road, Jinan, 250014, China.
Chenzhao MaDepartment of Ophthalmology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, #107 Wenhuaxi Road, Jinan, 250014, China.
Yantao WeiZhongshan Ophthalmic Center, Sun Yat-Sen University, WHO Collaborating Centre for Eye Care and Vision, State Key Laboratory of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, #7 Jinsui Road, Guangzhou, 510060, China. weiyantao75@126.com.
Jiawei WangDepartment of Ophthalmology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, #107 Wenhuaxi Road, Jinan, 250014, China. jiaweieye@sdu.edu.cn.
Jianqiao LiDepartment of Ophthalmology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, #107 Wenhuaxi Road, Jinan, 250014, China. 18560087118@163.com.

Funding

National Natural Science Foundation of China 82471090Natural Science Foundation of Shandong Province ZR2023MH139
6 · The paper itself

Abstract

This study aimed to explore the effects of AS-252424, a selective acyl-CoA synthetase long-chain family member 4 (ACSL4) inhibitor, against retinal ischemia-reperfusion (IR) injury and to elucidate the underlying mechanisms. A mouse model of retinal IR was established, and AS-252424 was administered intravitreally to assess its neuroprotective effect. Retinal ganglion cell (RGC) survival was evaluated by immunofluorescence. Retinal morphology and function were assessed by hematoxylin and eosin staining and electroretinography. Inner retinal neurons were analyzed for morphology and density by immunofluorescence. Expression, localization, and enzymatic activity of ACSL4 were measured by Western blot, immunofluorescence, and ELISA. Ferroptotic lipid peroxidation and oxidative stress were evaluated using malondialdehyde assay, 4-hydroxynonenal immunolabeling, C11-BODIPY 581/591, dihydroethidium probes, and glutathione quantification. Our results confirmed the localization of ACSL4 in human glaucomatous RGCs, with a similar localization pattern observed in mouse retinas. Furthermore, we demonstrated that ACSL4 expression reached its peak on day 1 after IR in mouse retinas. AS-252424 treatment significantly reduced RGC loss after IR. Importantly, AS-252424 achieved comparable RGC protection to Fer-1 at a lower concentration. We also found that AS-252424 preserved inner retinal structural integrity and alleviated edema after IR, as evidenced by quantitative analysis of individual retinal layer thickness. Functionally, AS-252424 significantly restored the amplitudes of the a-wave, b-wave, oscillatory potentials, and photopic negative response. Mechanistically, AS-252424 lowered arachidonic acid-CoA levels and inhibited lipid peroxidation in retinal RGCs after IR, thereby mitigating ferroptotic cell death. AS-252424 can significantly protect retinal structure and function after IR. The underlying mechanism involves the inhibition of ACSL4-mediated ferroptosis. Targeting ACSL4 represents a promising neuroprotective strategy to preserve visual function in ischemic retinopathy.

Indexed as

Coenzyme A LigasesFerroptosisNeuroprotective AgentsReperfusion InjuryRetinaRetinal Ganglion CellsVision, OcularAnimalsHumansLipid PeroxidationLong-Chain-Fatty-Acid-CoA LigaseMaleMiceMice, Inbred C57BLOxidative StressAcsl4 protein, mouseCoenzyme A LigasesLong-Chain-Fatty-Acid-CoA LigaseNeuroprotective AgentsACSL4AS-252424NeuroprotectionRetinal ischemia–reperfusion

Identifiers

PMID41649692

What Socratic holds

Textmetadata
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Registered trials

None linked

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 Socratic graph.