Evidence map›Paper›PMID 40892030›Full record

ArticleActa ophthalmologica2026

A model for de novo pigmentation of amelanotic retinal pigment epithelial cells.

Santosh Gupta, Lyubomyr Lytvynchuk, Taras Ardan, Hana Studenovska, Georgina Faura, Lars Eide, Ljubo Znaor, Slaven Erceg, Knut Stieger, Jan Motlik and 1 more

Abstract read
In one paragraph

Article in Acta ophthalmologica, 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

11 authors.

Santosh GuptaCenter for eye Research and Innovative Diagnostics, Department of Ophthalmology, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.ORCID https://orcid.org/0000-0003-1733-7382
Lyubomyr LytvynchukDepartment of Ophthalmology, Justus Liebig University Giessen, University Hospital Giessen and Marburg GmbH, Giessen, Germany.
Taras ArdanInstitute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Libechov, Czech Republic.ORCID https://orcid.org/0000-0002-4354-8354
Hana StudenovskaInstitute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Georgina FauraDepartment of Medical Biochemistry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Lars EideDepartment of Medical Biochemistry, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Ljubo ZnaorDepartment of Ophthalmology, University of Split School of Medicine and University Hospital of Split, Split, Croatia.
Slaven ErcegResearch Center 'Principe Felipe', Stem Cell Therapies in Neurodegenerative Diseases Laboratory, Valencia, Spain.
Knut StiegerDepartment of Ophthalmology, Justus Liebig University Giessen, University Hospital Giessen and Marburg GmbH, Giessen, Germany.ORCID https://orcid.org/0000-0002-8298-5629
Jan MotlikInstitute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, Libechov, Czech Republic.
Goran PetrovskiCenter for eye Research and Innovative Diagnostics, Department of Ophthalmology, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.ORCID https://orcid.org/0000-0003-2905-9252

Funding

European Union's Horizon 2020 801133IAPG institutional support RVO 67985904Johannes Amos Comenius Programme CZ.02.01.01/00/22_008/0004562Marie Skłodowska-Curie grant 18-04393SNorway Grants and Technology Agency of the Czech Republic TO01000107
6 · The paper itself

Abstract

purposeRetinal Pigment Epithelial (RPE) cells perform critical functions in the visual cycle. Their melanin pigmentation, which is organized into specialized compartments - melanosomes, is highly critical for proper vision. A chemical method to induce pigmentation in a non-pigmented model of ARPE-19 cells was applied using L-DOPA as a repurposed drug from the current treatment of Parkinson's disease.

methodsL-DOPA was optimized for its toxic effect on ARPE-19 cells along with pigmentation development. Gene expression and immunocytochemistry confirmed upregulation of melanogenesis-related genes and proteins. Melanosomes were characterized by TEM.

resultsWe found 1000 μM L-DOPA to induce pigmentation of ARPE-19 cells by Day 3, and achieve full pigmentation by Day 5. By Day 5, L-DOPA at 1000 μM induced mitochondrial and nuclear DNA damage. However, the gene expression of RPE-specific markers (tyrosinase, TYRP1, CRALBP, PEDF) was significantly different in L-DOPA-treated ARPE-19 cells compared to non-treated ones. Positive expression for Tyrosinase enzyme was confirmed by ICC on both Day 3 and Day 5 of L-DOPA treatment. Transmission electron microscopy showed the de novo melanosome formation with ultrastructural features of various stages of maturity (Stage I to IV), apical-basal polarity and melanosome localization on the apical side of the L-DOPA-treated ARPE-19 cells.

conclusionOur study showed that L-DOPA treatment could induce de novo melanosome formation in amelanotic RPEs. We propose a newer approach of developing an ex vivo model for de novo pigmentation of RPE cells with cell-specific modification and culture condition optimization.

Indexed as

LevodopaMelaninsPigmentationRetinal Pigment EpitheliumCells, CulturedEye ProteinsHumansImmunohistochemistryMelanosomesMicroscopy, Electron, TransmissionEye ProteinsLevodopaMelaninsin vitro modelL‐DOPAmelanosomespigmentationRPE

Identifiers

PMID40892030
PMCPMC12888947

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Registered trials

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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.