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PreprintCC BY-NC-NDbioRxiv

Transcriptomic profiling of normal and glaucomatous trabecular meshwork cells in a tissue-like soft ECM environment

  • Rajanya Ghosh1,2
  • Rachel Hadvina3
  • Ana N. Strat1,4
  • Preethi S. Ganapathy1,4
  • W. Daniel Stamer5
  • Kate E. Keller6
  • Yutao Liu3,7
  • Samuel Herberg1,2,8,9,10
10 affiliations
  1. 1Department of Ophthalmology and Visual Sciences, Center for Vision Research, SUNY Upstate Medical University, Syracuse, NY 13210, USA
  2. 2Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA
  3. 3Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA
  4. 4Department of Neuroscience, SUNY Upstate Medical University, Syracuse, NY 13210, USA
  5. 5Department of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27705, USA
  6. 6Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA
  7. 7Department of Ophthalmology, Mayo Clinic, Rochester, MN 55905, USA
  8. 8Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA
  9. 9BioInspired Institute, Syracuse University, Syracuse, NY 13244, USA
  10. 10Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USA
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Abstract

Purpose. Trabecular meshwork (TM) dysfunction contributes to the elevated intraocular pressure in primary open-angle glaucoma. To better understand the molecular signature distinguishing glaucomatous from normal TM cells, we interrogated their genome-wide transcriptomic differences in a tissue-like soft extracellular matrix (ECM) microenvironment. Methods. Primary human glaucomatous and normal TM cell strains (N = 5 each) from three independent laboratories were plated on bioengineered collagen type I/hyaluronic acid/elastin-like polypeptide ECM hydrogels in 10% FBS media for 4-5 days, then serum-free media for 2 days. Cell-laden hydrogels were homogenized in TRIzol for RNA isolation, quality assessment, and library preparation, followed by paired-end 100-bp Illumina sequencing. Differential expression was assessed using DESeq2, including glaucoma status, originating laboratory, and donor age/sex in the model. Differentially expressed genes (DEGs) were defined as p < 0.05 and |fold change| [≥] 2, followed by Gene Ontology (GO) enrichment and QIAGEN Ingenuity Pathway Analysis (IPA). Results. In total, 588 DEGs distinguished the glaucomatous from the normal TM transcriptome (393 up-regulated in glaucomatous TM; 195 up-regulated in normal TM, i.e., down-regulated in glaucomatous TM). GO and IPA causal analyses revealed three coordinated disease programs: (i) TGF-{beta}/Wnt-driven ECM remodeling and fibrosis, (ii) NF-{kappa}B-associated inflammation, and (iii) a hypoxia/metabolic-stress program linked to p300/CREBBP chromatin co-activation. Conclusions. These data define a transcriptomic signature of glaucomatous TM cells when cultured in a soft physiologic ECM microenvironment, independent of the originating laboratory, with three mechanistic axes (ECM/fibrosis, inflammation, hypoxia/metabolism), and nominate p300 (encoded by EP300) as a candidate upstream node integrating these programs.

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Cite

BibTeXRIS
BibTeX
@misc{ghosh2026transcriptomic,
  title = {{Transcriptomic profiling of normal and glaucomatous trabecular meshwork cells in a tissue-like soft ECM environment}},
  author = {Rajanya Ghosh and Rachel Hadvina and Ana N. Strat and Preethi S. Ganapathy and W. Daniel Stamer and Kate E. Keller and Yutao Liu and Samuel Herberg},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.26.761819},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.26.761819v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - Transcriptomic profiling of normal and glaucomatous trabecular meshwork cells in a tissue-like soft ECM environment
AU  - Rajanya Ghosh
AU  - Rachel Hadvina
AU  - Ana N. Strat
AU  - Preethi S. Ganapathy
AU  - W. Daniel Stamer
AU  - Kate E. Keller
AU  - Yutao Liu
AU  - Samuel Herberg
PY  - 2026
DA  - 2026/10/26
PB  - bioRxiv
DO  - 10.64898/2026.10.26.761819
UR  - https://www.biorxiv.org/content/10.64898/2026.10.26.761819v1
AB  - Purpose. Trabecular meshwork (TM) dysfunction contributes to the elevated intraocular pressure in primary open-angle glaucoma. To better understand the molecular signature distinguishing glaucomatous from normal TM cells, we interrogated their genome-wide transcriptomic differences in a tissue-like soft extracellular matrix (ECM) microenvironment. Methods. Primary human glaucomatous and normal TM cell strains (N = 5 each) from three independent laboratories were plated on bioengineered collagen type I/hyaluronic acid/elastin-like polypeptide ECM hydrogels in 10% FBS media for 4-5 days, then serum-free media for 2 days. Cell-laden hydrogels were homogenized in TRIzol for RNA isolation, quality assessment, and library preparation, followed by paired-end 100-bp Illumina sequencing. Differential expression was assessed using DESeq2, including glaucoma status, originating laboratory, and donor age/sex in the model. Differentially expressed genes (DEGs) were defined as p < 0.05 and |fold change| [≥] 2, followed by Gene Ontology (GO) enrichment and QIAGEN Ingenuity Pathway Analysis (IPA). Results. In total, 588 DEGs distinguished the glaucomatous from the normal TM transcriptome (393 up-regulated in glaucomatous TM; 195 up-regulated in normal TM, i.e., down-regulated in glaucomatous TM). GO and IPA causal analyses revealed three coordinated disease programs: (i) TGF-{beta}/Wnt-driven ECM remodeling and fibrosis, (ii) NF-{kappa}B-associated inflammation, and (iii) a hypoxia/metabolic-stress program linked to p300/CREBBP chromatin co-activation. Conclusions. These data define a transcriptomic signature of glaucomatous TM cells when cultured in a soft physiologic ECM microenvironment, independent of the originating laboratory, with three mechanistic axes (ECM/fibrosis, inflammation, hypoxia/metabolism), and nominate p300 (encoded by EP300) as a candidate upstream node integrating these programs.
SN  - 2692-8205
ER  -