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Transcriptomic signatures associated with regenerative wound vs. fibrotic repair outcomes to lens post-cataract surgery wounding

ABSTRACT: RNAseq analysis was used to determine the transcriptomic changes associated with regenerative vs. fibrotic repair to lens injury. Using an ex vivo post-cataract surgery model, we can follow two distinct outcomes to lens injury: 1) A regenerative wound healing response that ensues across the cell-denuded lens capsule basement membrane (BM), culminating in wound closure on Day 3 (D3) post-injury. 2) Induction of fibrosis, which occurs when a wound healing response occurs off the lens capsule, termed the extracapsular zone (ECZ), where transition to a fibrotic phenotype occurs on day 3 post-injury. Here, we report the changes in the transcriptome that occur on D1, D2, and D3 post-injury, a period that covers wound healing across the BM and time points prior to (D1, D2) and after induction of the fibrotic phenotype (D3). Our data provides a molecular map for understanding the gene changes associated with navigating normal and pathological outcomes to lens injury.

ORGANISM(S): Gallus gallus

PROVIDER: GSE298481 | GEO | 2025/06/02

REPOSITORIES: GEO

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Project description:While considerable progress has been made towards understanding the complex processes and pathways that regulate human wound healing, regenerative medicine has been unable to develop therapies that coax the natural wound environment to heal scar-free. The inability to induce perfect skin regeneration stems partly from our limited understanding of how scar-free healing occurs in a natural setting. Here we have investigated the wound repair process in adult axolotls and demonstrate that they are capable of perfectly repairing full thickness excisional wounds made on the flank. In the context of mammalian wound repair, our findings reveal a substantial reduction in hemostasis, reduced neutrophil infiltration and a relatively long delay in production of new extracellular matrix (ECM) during scar-free healing. Additionally, we test the hypothesis that metamorphosis leads to scarring and instead show that terrestrial axolotls also heal scar-free, albeit at a slower rate. Analysis of newly forming dermal ECM suggests that low levels of fibronectin and high levels of tenascin-C promote regeneration in lieu of scarring. Lastly, a genetic analysis during wound healing comparing epidermis between aquatic and terrestrial axolotls suggests that matrix metalloproteinases may regulate the fibrotic response. Our findings outline a blueprint to understand the cellular and molecular mechanisms coordinating scar-free healing that will be useful towards elucidating new regenerative therapies targeting fibrosis and wound repair. We used microarray analysis to determine the gene expression changes that take place during scar free wound healing in aquatic and terrestrial axolotl salamanders. Epidermal tissue was harvested using a 4mm biopsy punch. Two wounds were made along the flank and posterior to the forelimbs. Harvested epidermis was pooled for each animal. Four biological replicates were collected from uninjured epidermis (D0) and at 1, 3, and 7 days post injury.

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Transcriptomic signatures associated with regenerative wound vs. fibrotic repair outcomes to lens post-cataract surgery wounding

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