Evidence map›Paper›PMID 40548631›Full record

ArticleInvestigative ophthalmology & visual science2025

Small-Molecule Inhibition of the Hippo Pathway Induces Regeneration of Retinal Pigment Epithelium.

Erik A Souverein, Sanyukta Oak, Zachary Fouladian, Mark W Reid, G Esteban Fernandez, Andrew Salas, Jennifer G Aparicio, Aaron Nagiel, Ksenia Gnedeva

Abstract read
PubMed Full text at PMC Publisher
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. 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

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

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

9 authors.

Erik A SouvereinKeck School of Medicine of USC, University of Southern California, Los Angeles, California, United States.
Sanyukta OakUSC Caruso Department of Otolaryngology - Head and Neck Surgery, Keck School of Medicine of USC, University of Southern California, Los Angeles, California, United States.
Zachary FouladianKeck School of Medicine of USC, University of Southern California, Los Angeles, California, United States.
Mark W ReidThe Vision Center, Department of Surgery, Children's Hospital Los Angeles, Los Angeles, California, United States.
G Esteban FernandezThe Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, United States.
Andrew SalasThe Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, United States.
Jennifer G AparicioThe Vision Center, Department of Surgery, Children's Hospital Los Angeles, Los Angeles, California, United States.
Aaron NagielThe Vision Center, Department of Surgery, Children's Hospital Los Angeles, Los Angeles, California, United States.
Ksenia GnedevaUSC Caruso Department of Otolaryngology - Head and Neck Surgery, Keck School of Medicine of USC, University of Southern California, Los Angeles, California, United States.

Funding

Ophthalmic Therapeutics Engineering CoreP30EY029220 · NEI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Mahnaz Shahidi · 2018 to 2026
$6.5M
Development and Maintenance of the Human Photoreceptor-Bipolar Cell Synapse.K08EY030924 · NEI · CHILDREN'S HOSPITAL OF LOS ANGELES · PI NAGIEL, AARON · 2020 to 2024
$1.1M
NEI NIH HHS K08 EY030924NEI NIH HHS P30 EY029220
6 · The paper itself

Abstract

Purpose: To investigate whether Hippo pathway inhibition via a novel Lats kinase inhibitor (LKI) induces regeneration of retinal pigment epithelium (RPE). Methods: An in vitro scratch "injury" on confluent RPE monolayers was produced using the Woundmaker Tool. A 6×6 grid of laser spots was delivered to the central retinae of Dutch Belted rabbits via indirect laser. Following laser injury, eyes received 50 µL intravitreal LKI or vehicle. Fundus photography and optical coherence tomography (OCT) were performed prior to sacrifice for immunohistological analyses. Results: In vitro RPE demonstrated accelerated wound healing 24 to 96 hours after injury with LKI versus control treatment (P < 0.0001). In the in vivo rabbit model of retinal degeneration, laser spots in LKI-injected eyes demonstrated hyperpigmentation and RPE layer thickening with shadowing on OCT beginning at 1 week after treatment. There was a marked increase in RPE cross-sectional area (P < 0.0001) and percentage of Ki67+ RPE and Müller glia (P < 0.001), specifically at the laser spots. At 4 weeks, the increase in RPE cross-sectional area persisted (P < 0.001), but Ki67+ cells were no longer observed within the RPE (P = 0.36) or Müller glia (P = 0.48). The response was limited to the damaged regions, and there was no proliferation seen in the intact retina in either control or LKI-treated eyes. Conclusions: Hippo pathway inhibition via a novel LKI promotes wound healing and RPE proliferation in RPE monolayers in vitro. In a rabbit model of geographic atrophy, LKI treatment facilitated robust RPE regeneration and Müller glia proliferation specifically at the sites of injury.

Indexed as

Protein Serine-Threonine KinasesRegenerationRetinal DegenerationRetinal Pigment EpitheliumAnimalsCell ProliferationCells, CulturedDisease Models, AnimalHippo Signaling PathwayIntravitreal InjectionsRabbitsSignal TransductionTomography, Optical CoherenceWound HealingProtein Serine-Threonine Kinases

Identifiers

PMID40548631
PMCPMC12186839

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.