{
  "abstract": "Background. ARPE-19 cells are widely used to investigate and model retinal pigmented epithelium (RPE). Naïve ARPE-19 cells do not fully replicate RPE features. Previous reports show that under defined conditions, ARPE-19 differentiate towards an RPE phenotype, with protocols relying on prolonged or shorter-term cultures, the latter of which do not achieve full pigmentation. In particular, bioenergetics and mitochondrial dynamics have been assessed in a limited manner to date. The present work aims to characterise ARPE-19 under long-term physiologically relevant phenotype-inducing culture conditions, monitoring the timeline of RPE phenotype acquisition, with a focus on mitochondrial function and bioenergetics alongside structural and functional markers. Methods. Low passage ARPE-19 were cultured for 4 months using low-serum, pyruvate and nicotinamide-supplemented DMEM. Monthly assessments measured pigmentation, TER, gene/protein expression, mitochondrial parameters, and metabolism. Results. ARPE-19 acquired relevant features early (1 month), including polarisation, expression of visual cycle and mitochondrial dynamic drivers, as well as increases in mitochondrial potential, mass/area and branching. Melanin accumulation was increased beginning at 1 month. Bioenergetic assays revealed a shift towards increased reliance on oxidative phosphorylation compared to glycolysis. Conclusions. Under these conditions, ARPE-19 acquired specific RPE features supporting functional assays after 1 month. Time-dependent accumulation of RPE-like features suggests that, for certain applications, later differentiation times are suitable. Appropriately differentiated ARPE-19 are a viable model to study key RPE physiological functions when accompanied by evidence of specific phenotypic and metabolic characterization.",
  "abstract_shown": true,
  "affiliations": [
    "Ocular Molecular Biology and Mechanisms of Disease Group, School of Biological and Chemical Sciences, Manchester Metropolitan University, Manchester M1 5GD, UK",
    "Department of Biology, Edge Hill University, Ormskirk L39 4QP, UK",
    "Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ioan V. Matei",
      "orcid": "0000-0001-5303-0316"
    },
    {
      "affs": [
        1
      ],
      "name": "Daniel Grimes"
    },
    {
      "affs": [
        0
      ],
      "name": "Gunticha Suwanmanee",
      "orcid": "0009-0001-7061-0969"
    },
    {
      "affs": [
        2
      ],
      "name": "James Bagnall"
    },
    {
      "affs": [
        2
      ],
      "name": "David G. Spiller"
    },
    {
      "affs": [
        0
      ],
      "name": "Luminita Paraoan",
      "orcid": "0000-0001-7568-7116"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dqkfvcvdkw1nf.bib",
  "cited_by": 0,
  "doi": "10.3390/cells15201846",
  "fulltext_url": "https://europepmc.org/articles/PMC13702982",
  "id": "dqkfvcvdkw1nf",
  "issns": [
    "2073-4409"
  ],
  "landing_url": "https://www.mdpi.com/2073-4409/15/20/1846",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2731|Retinal Diseases and Treatments"
    ]
  ],
  "openalex": "W7221571549",
  "pdf_url": "https://europepmc.org/articles/PMC13702982?pdf=render",
  "pmcid": "PMC13702982",
  "pmid": "42929819",
  "published": "2026-10-12",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/dqkfvcvdkw1nf.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:02Z",
      "native_id": "10.3390/cells15201846",
      "source": "crossref",
      "url": "https://www.mdpi.com/2073-4409/15/20/1846"
    },
    {
      "first_seen": "2026-10-30T12:22:01Z",
      "native_id": "MED:42929819",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42929819"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:2073-4409",
      "subfield": "cell-biology"
    }
  ],
  "title": "Timeline of Achieving a Differentiated RPE Phenotype and Specialised Metabolism of ARPE-19 Cells Under Physiologically Relevant-Inducing Culture Conditions",
  "title_text": "Timeline of Achieving a Differentiated RPE Phenotype and Specialised Metabolism of ARPE-19 Cells Under Physiologically Relevant-Inducing Culture Conditions",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:01Z",
  "url": "https://research.draconitic.com/paper/dqkfvcvdkw1nf",
  "venue": "Cells",
  "versions": []
}