Evidence map›Paper›PMID 41688739›Full record

ArticleExperimental & molecular medicine2026

Erythropoiesis-inosine metabolic axis failure underlying retinal neurodegeneration in glaucoma: novel diagnoses and therapies.

Yuyu Chou, Wuping Liu, Yanxiu Li, Changhan Chen, Cheng Luo, Shiping Shen, Piaoyu Dai, Lemeng Feng, Wenhao Xiao, Yiyan Wang and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Experimental & molecular medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

19 authors.

Yuyu ChouEye Center of Xiangya Hospital, Central South University, Changsha, China.
Wuping LiuNational Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, China.
Yanxiu LiEye Center of Xiangya Hospital, Central South University, Changsha, China.
Changhan ChenNational Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, China.ORCID http://orcid.org/0009-0009-8342-5680
Cheng LuoNational Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, China.
Shiping ShenNational Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, China.
Piaoyu DaiNational Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, China.
Lemeng FengEye Center of Xiangya Hospital, Central South University, Changsha, China.
Wenhao XiaoNational Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, China.
Yiyan WangNational Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, China.
Juncheng WangNational Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, China.
Linlin WanNational Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, China.
Zhiyu YangNational Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, China.
Tingting XieNational Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, China.
Yujin ZhangNational Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, China.
Rodney E KellemsDepartment of Biochemistry and Molecular Biology, The University of Texas McGovern Medical School, Houston, TX, USA.
Weitao SongEye Center of Xiangya Hospital, Central South University, Changsha, China.
Xiaobo XiaEye Center of Xiangya Hospital, Central South University, Changsha, China. xbxia21@csu.edu.cn.ORCID http://orcid.org/0000-0003-1720-7860
Yang XiaNational Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, China. yang.xia1106@csu.edu.cn.

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82401260
6 · The paper itself

Abstract

Glaucoma, long considered an ocular-limited, age-dependent and hypoxia-driven neurodegeneration, is here reframed as a systemic erythroid-inosine axis failure that originates in the bone marrow yet culminates in retinal ganglion cell (RGC) death. By mining UK Biobank datasets (n = 127,028) and validating our findings in an independent clinical cohort (n = 178), we reveal that glaucoma is preceded by dyserythropoiesis and a compensatory, AMPK-driven metabolic rewiring of mature erythrocytes that hypercatabolizes inosine to enhance oxygen unloading. This adaptation collapses when accelerated erythrocyte inosine metabolism drains systemic pools, starving high-energy demand hematopoietic progenitors, driving retinal microenvironment hypoxia and accelerating RGC loss. Genetic ablation of murine erythroid equilibrative nucleoside transporter 1 (ENT1) recapitulates the hallmark features of patients with glaucoma, including impaired erythropoiesis, reduced oxygen delivery, retinal hypoxia and RGC apoptosis in both age and intraocular pressure-induced glaucoma models. Conversely, inosine repletion reconstitutes erythroid output, restores oxygen delivery from mature erythrocytes and halts neurodegeneration in inducible glaucoma models. A ten-metabolite erythrocyte signature centered on inosine metabolism offers diagnostic potential. Altogether, our work redefines glaucoma as the first treatable systemic erythroid-driven hypoxic syndrome, positioning inosine as a pleiotropic metabolic rescue factor for neurodegeneration and a powerful biomarker for intercepting hypoxia-driven pathologies across organs.

Indexed as

ErythropoiesisGlaucomaInosineRetinal DegenerationAnimalsDisease Models, AnimalEquilibrative Nucleoside Transporter 1ErythrocytesHumansMiceRetinal Ganglion CellsEquilibrative Nucleoside Transporter 1Inosine

Identifiers

PMID41688739
PMCPMC12992561

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.