Evidence map›Paper›PMID 42616788›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2026

A human pluripotent stem cell triculture platform to elucidate microglial regulation of retinal ganglion cells in neuroinflammation.

Jade Harkin, Cátia Gomes, Reham Afify, Shruti V Patil, Shelby M Hetzer, Kaylee D Tutrow, Kiersten H Peña, Aaron Baker, Sailee S Lavekar, Kang-Chieh Huang and 1 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. 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
  2. Neuroinflammation in glaucoma: a myriad of cellular pathways and players.Mammalian genome : official journal of the International Mammalian Genome Society · 2026
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Jade HarkinDepartment of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202.
Cátia GomesStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202.ORCID 0000-0001-8491-6822
Reham AfifyStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202.
Shruti V PatilStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202.
Shelby M HetzerStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202.
Kaylee D TutrowStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202.
Kiersten H PeñaStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202.ORCID 0009-0009-3490-6154
Aaron BakerStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202.
Sailee S LavekarStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202.ORCID 0000-0002-1629-3536
Kang-Chieh HuangStark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202.
Jason S MeyerDepartment of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202.ORCID 0000-0001-9037-6033

Funding

Overcoming Barriers to retinal ganglion cell replacement in experimental glaucomaU24EY033269 · NEI · INDIANA UNIVERSITY INDIANAPOLIS · PI FORTUNE, BRAD, MEYER, JASON STEPHEN · 2021 to 2025
$7.0M
Establishing a human cellular model of retinal ganglion cell compartmentalization in neurodegeneration and neuroinflammationR01EY033022 · NEI · INDIANA UNIVERSITY INDIANAPOLIS · PI Jason Stephen Meyer · 2021 to 2026
$2.7M
BrightFocus Foundation (BFF) G2020369BrightFocus Foundation (BFF) G2022003FGilbert Family Foundation (GFF) 923016HHS | NIH | National Eye Institute (NEI) R01EY033022HHS | NIH | National Eye Institute (NEI) U24EY033269NEI NIH HHS R01 EY033022NEI NIH HHS U24 EY033269
6 · The paper itself

Abstract

Optic neuropathies, including glaucoma, are characterized by the progressive degeneration of retinal ganglion cells (RGCs), ultimately leading to irreversible vision loss. Increasing evidence implicates microglia, the resident immune cells of the central nervous system, as key modulators of RGC health and disease progression. However, the precise mechanisms by which microglia influence RGCs remain poorly understood, particularly in the human context. In this study, we established human pluripotent stem cell-derived coculture systems incorporating microglia, astrocytes, and RGCs to explore how microglia shape RGC growth and maturation under physiological conditions. We first examined the impact of homeostatic microglia on RGCs in both coculture and triculture systems, revealing distinct influences of cell types in coculture compared to when they were grown individually. We then modeled inflammatory states by activating microglia with lipopolysaccharide and evaluated their effects on RGCs both directly and in the context of astrocyte coculture. This stepwise, reductionist approach enabled us to dissect the cellular interactions driving RGC vulnerability in inflammatory conditions relevant to optic neuropathies. Our findings provide insight into the complex neuroimmune landscape that underlies RGC degeneration and identify key pathways that may serve as therapeutic targets across a range of optic nerve diseases.

Indexed as

MicrogliaNeuroinflammatory DiseasesPluripotent Stem CellsRetinal Ganglion CellsAstrocytesCoculture TechniquesHumansInflammationLipopolysaccharidesLipopolysaccharidesmicroglianeuroinflammationretinaretinal ganglion cellstem cell

Identifiers

PMID42616788
PMCPMC13506028

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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.