Evidence map›Paper›PMID 40249603›Full record

ArticleInvestigative ophthalmology & visual science2025

Pax6 Directly Regulates the Raver2/sFlt-1 Expression in Corneal Epithelial Cells to Maintain the Cornea's Avascular Privilege.

Haiqi Xiao, Li Hu, Xiongshi Lin, Linchang Liu, Xing Dong, Liting Yang, Ying Liu, Zhichong Wang, Ying Tian, Shuangyong Wang

Abstract 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. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
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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

10 authors.

Haiqi XiaoDepartment of Ophthalmology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Li HuDepartment of Ophthalmology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Xiongshi LinDepartment of Ophthalmology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Linchang LiuDepartment of Ophthalmology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Xing DongThe Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Liting YangDepartment of Ophthalmology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Ying LiuState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Zhichong WangState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Ying TianDepartment of Ophthalmology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Shuangyong WangDepartment of Ophthalmology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: This study aimed to elucidate how Pax6 directly regulates Raver2 and sFlt-1 expression in corneal epithelial cells to maintain the cornea's avascular privilege during normal development. Methods: The expression levels of Pax6, Raver2, and sFlt-1 in both the mouse cornea and human corneal epithelial cell line (HCE-T) were evaluated. Changes in Raver2 and sFlt-1 expression following Pax6 knockdown were also assessed. Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR), electrophoresis mobility shift assay (EMSA), and dual-luciferase reporter (DLR) assay were conducted to ascertain the regulatory relationship between Pax6 and Raver2. The impact on vascular endothelial cell proliferation, migration, and tube formation was examined after coculturing with siPax6-HCE-T conditioned culture medium. Additionally, corneal neovascularization (CoNV) was monitored following corneal epithelial scraping or injection of the AAV-siPax6 vector into the limbus. Results: Pax6, Raver2, and sFlt-1 were highly expressed in both HCE-T cells and normal mouse corneal epithelial layer. Interference with Pax6 expression resulted in decreased levels of Raver2 and sFlt-1 both in vivo and in vitro. TFBS1 and TFBS2 in the Raver2 promoter region were identified as potential Pax6 binding sites. ChIP-qPCR and EMSA assays confirmed the direct interaction between Pax6 and Raver2. The DLR assay demonstrated that Pax6 binding to the TFBS1 and TFBS2 regulated Raver2 expression. Vascular endothelial cell proliferation, migration, and tube formation were enhanced when cocultured with siPax6-HCE-T conditioned culture medium. CoNV progressed after corneal epithelial scraping and AAV-siPax6 vector injection. Conclusions: Pax6 directly regulates Raver2/sFlt-1 expression in corneal epithelial cells, thus preserving the cornea's avascular privilege during normal development.

Indexed as

Epithelium, CornealGene Expression RegulationPAX6 Transcription FactorVascular Endothelial Growth Factor Receptor-1AnimalsCell MovementCell ProliferationCells, CulturedChromatin ImmunoprecipitationCorneal NeovascularizationHumansMiceMice, Inbred C57BLReal-Time Polymerase Chain ReactionPAX6 protein, humanPax6 protein, mousePAX6 Transcription FactorVascular Endothelial Growth Factor Receptor-1

Identifiers

PMID40249603
PMCPMC12013671

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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.