Evidence map›Paper›PMID 25030175›Full record

ArticleNature2014

WNT7A and PAX6 define corneal epithelium homeostasis and pathogenesis.

Hong Ouyang, Yuanchao Xue, Ying Lin, Xiaohui Zhang, Lei Xi, Sherrina Patel, Huimin Cai, Jing Luo, Meixia Zhang, Ming Zhang and 15 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02148016 (Corneal Epithelium Repair and Therapy Using Autologous Limbal Stem Cell Transplantation), which is not on this map. Cited by 137 papers.

0numbers the graph read from it
0cells of the map it votes in
137citing 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.

NCT02148016 phase1 / phase2unknown statusnot on this map

Corneal Epithelium Repair and Therapy Using Autologous Limbal Stem Cell Transplantation

TypeinterventionalSponsorSun Yat-sen UniversityRan2012 to 2014Enrolled30ConditionsCorneal Disease, Pterygium, Myopia, HyperopiaArmsLSCs and amniotic membrane (Modified Technique), Amniotic membrane only (Traditional Technique), PRK, LSCs, and amniotic membrane (Modified Technique), PRK only (Traditional Technique), Levofloxacin
3 · Its place in the literature

Who cites it

137 citing papers in PubMed.

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  12. MYEOV Is a Novel Marker of Differentiated Corneal Epithelium.Investigative ophthalmology & visual science · 2025
    Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
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77 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors.

Hong Ouyang1] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [2] Department of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Yuanchao XueDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92093, USA.
Ying Lin1] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [2] Department of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Xiaohui Zhang1] Department of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing 100730, China (X.Z.); Department of Ophthalmology, Shengjing Hospital of China Medical University, Shenyang 110004, China (Y.Y.).
Lei Xi1] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [2] Department of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Sherrina PatelDepartment of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Huimin Cai1] Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, China [2] Guangzhou KangRui Biological Pharmaceutical Technology Company Ltd., Guangzhou 510005, China.
Jing LuoDepartment of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Meixia ZhangMolecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, China.
Ming ZhangMolecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, China.
Yang Yang1] Department of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing 100730, China (X.Z.); Department of Ophthalmology, Shengjing Hospital of China Medical University, Shenyang 110004, China (Y.Y.).
Gen LiMolecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, China.
Hairi LiDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92093, USA.
Wei JiangMolecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, China.
Emily YehDepartment of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Jonathan LinDepartment of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Michelle PeiDepartment of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Jin ZhuDepartment of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA.
Guiqun CaoMolecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, China.
Liangfang Zhang1] Department of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Nanoengineering, University of California San Diego, La Jolla, California 92093, USA.
Benjamin Yu1] Department of Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Institute for Genomic Medicine, University of California San Diego, La Jolla, California 92093, USA.
Shaochen Chen1] Department of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Nanoengineering, University of California San Diego, La Jolla, California 92093, USA.
Xiang-Dong Fu1] Department of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [2] Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California 92093, USA [3] Institute for Genomic Medicine, University of California San Diego, La Jolla, California 92093, USA.
Yizhi LiuState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
Kang Zhang1] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China [2] Department of Ophthalmology, and Biomaterial and Tissue Engineering Center of Institute of Engineering in Medicine, University of California San Diego, La Jolla, California 92093, USA [3] Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Sichuan 610041, China [4] Institute for Genomic Medicine, University of California San Diego, La Jolla, California 92093, USA [5] Veterans Administration Healthcare System, San Diego, California 92093, USA.

Funding

FUNCTION &REGULATION OF THE HUMAN SPLICING FACTOR SC35R01GM049369 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FU, XIANG-DONG · 1993 to 2018
$7.2M
Regeneration of Retinal Neurons by Chemically Induced Reprogramming of Muller GliR01EY021374 · NEI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DING, SHENG, REH, THOMAS A · 2010 to 2014
$4.2M
Endoplasmic Reticulum Stress in Retinal DegenerationR01EY020846 · NEI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LIN, JONATHAN · 2010 to 2014
$1.9M
NEI NIH HHS R01 EY020846NEI NIH HHS R01 EY021374NIGMS NIH HHS GM049369NIGMS NIH HHS R01 GM049369
6 · The paper itself

Abstract

The surface of the cornea consists of a unique type of non-keratinized epithelial cells arranged in an orderly fashion, and this is essential for vision by maintaining transparency for light transmission. Cornea epithelial cells (CECs) undergo continuous renewal from limbal stem or progenitor cells (LSCs), and deficiency in LSCs or corneal epithelium--which turns cornea into a non-transparent, keratinized skin-like epithelium--causes corneal surface disease that leads to blindness in millions of people worldwide. How LSCs are maintained and differentiated into corneal epithelium in healthy individuals and which key molecular events are defective in patients have been largely unknown. Here we report establishment of an in vitro feeder-cell-free LSC expansion and three-dimensional corneal differentiation protocol in which we found that the transcription factors p63 (tumour protein 63) and PAX6 (paired box protein PAX6) act together to specify LSCs, and WNT7A controls corneal epithelium differentiation through PAX6. Loss of WNT7A or PAX6 induces LSCs into skin-like epithelium, a critical defect tightly linked to common human corneal diseases. Notably, transduction of PAX6 in skin epithelial stem cells is sufficient to convert them to LSC-like cells, and upon transplantation onto eyes in a rabbit corneal injury model, these reprogrammed cells are able to replenish CECs and repair damaged corneal surface. These findings suggest a central role of the WNT7A-PAX6 axis in corneal epithelial cell fate determination, and point to a new strategy for treating corneal surface diseases.

Indexed as

HomeostasisAnimalsCell DifferentiationCell LineageCorneal DiseasesDisease Models, AnimalEpithelium, CornealEye ProteinsHomeodomain ProteinsHumansLimbus CorneaeMalePaired Box Transcription FactorsPAX6 Transcription FactorRabbitsRepressor ProteinsEye ProteinsHomeodomain ProteinsPaired Box Transcription FactorsPAX6 protein, humanPAX6 Transcription FactorRepressor ProteinsTP63 protein, humanTranscription FactorsTumor Suppressor ProteinsWNT7A protein, humanWnt Proteins

Identifiers

PMID25030175
PMCPMC4610745

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Registered trials

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.