“Pliancy Genes” and the Eye’s Hidden Repair Code

Leon Wirz
Oct 13
4 min read

Published in Developmental Cell, February 2025 (St. Jude Children’s Research Hospital)

Introduction

Blindness and severe visual impairment affect over 2.2 billion people worldwide. In high-income countries such as Switzerland, the leading causes are age-related macular degeneration (AMD), diabetic retinopathy, and glaucoma. All diseases that progressively destroy retinal neurons.

Despite major pharmaceutical advances like Lucentis®, Beovu®, and Vabysmo®, current therapies only slow down degeneration; none can restore lost vision.

A new study published in Developmental Cell in 2025 by researchers at St. Jude Children’s Research Hospital uncovers a remarkable mechanism that could change that. The team identified so-called “pliancy genes” — silent but epigenetically primed genetic programs that allow retinal cells to respond faster and more effectively to stress or injury.

This suggests that our eyes may already contain a latent self-repair system — one that modern medicine could learn to activate.

The Core Discovery

The retina’s main support cells, Müller glia, act like caretakers: they stabilize neurons, recycle neurotransmitters, and maintain structure. In some species, like zebrafish, they can even regenerate neurons after injury. In humans, this regenerative capacity is dormant, but not gone.

Researchers discovered that human Müller glia harbor hundreds of genes whose DNA is “open” (accessible chromatin) but not normally expressed. These pliancy genes are essentially “unlocked emergency exits.” When the retina faces stress these genes can be switched on within hours to stabilize and protect the tissue.

Examples of retinal stress

Oxidative stress: excessive reactive oxygen species, as in diabetic retinopathy.
Inflammatory stress: viral or autoimmune inflammation (retinitis, uveitis).
Ischemic stress: oxygen deprivation during vascular occlusion or stroke.
Excitotoxicity: overactivation of neurons causing glutamate-induced damage.
Mechanical stress: elevated intraocular pressure in glaucoma.

How the Study Was Conducted

The researchers combined cutting-edge techniques:

Single-cell RNA sequencing (scRNA-seq) to profile gene activity across thousands of retinal cells.
ATAC-seq to identify open, transcription-ready regions of the genome.
Stress models (oxidative, inflammatory, temperature, and metabolic).
Functional manipulation of key epigenetic regulators via CRISPR-Cas9.

This integrated approach allowed the team to pinpoint exactly where pliancy genes reside and how they react to damage.

Key Findings

Hundreds of genes in Müller glia are “open” but silent — poised for activation.
When stressed, these genes activate within hours, initiating protective pathways.
The pliant chromatin state persists, acting as a form of cellular memory.
Re-activating pliancy regulators partially restored regenerative behavior in human retinal organoids.

Limitations of the Study

The work was primarily preclinical, using animal and in-vitro human models.
It remains unclear how much pliancy can be harnessed in aged or diseased human retinas.
The conversion from glia to neurons was only partial. Functional vision restoration in humans is still far off.
Epigenetic therapies carry risks of off-target activation and unpredictable gene expression changes.

Relevance for Switzerland

Switzerland is a world leader in ophthalmology and biotechnology. Basel-based Novartis and Roche dominate the retinal drug market, while academic centers such as EPFL, ETH Zürich, and USZ lead pioneering work in retinal gene therapy and neuroprosthetics.

If pliancy-based regeneration proves viable, Switzerland could play a central role in clinical translation — merging its expertise in precision medicine, biotech engineering, and health-economic innovation.

Potential Impacts of a Successful Therapy

If scientists can learn to safely reactivate pliancy genes, future therapies might help the retina defend and repair itself without external stem-cell transplants. Patients with early AMD or diabetic retinopathy could receive a targeted treatment that strengthens the retina’s stress response, slowing disease and preserving sight.

The broader implications are profound: such therapies could also inform regenerative approaches for the brain and spinal cord, where similar epigenetic programs exist.

From a financial standpoint, blindness costs Switzerland an estimated CHF 150 000 – 200 000 per patient over a lifetime. A therapy that reduces that burden even slightly could save hundreds of millions in healthcare expenditures while improving quality of life for thousands.

This represents a shift from managing decline to reawakening resilience, a paradigm change for ophthalmology, insurers, and society alike.

Risks and Ethical Considerations

Off-target activation of genes could trigger tumors or immune reactions.
Germline transmission of chromatin changes must be avoided.
Early therapies will be costly and may challenge current reimbursement systems.
Regulatory frameworks for epigenetic treatments are still evolving.

Overall Assessment

The discovery of pliancy genes marks a conceptual breakthrough: regeneration may not require adding new genes, but unlocking existing ones.

For Switzerland’s biotech ecosystem, this convergence of epigenetics, AI, and regenerative medicine opens an entirely new frontier — one that bridges basic molecular science and tangible healthcare impact.

If confirmed, pliancy-based therapies could transform how we treat vision loss and redefine what “repair” means in human biology.

What Comes Next

Validation in human retinal organoids and primate models.
Discovery of small molecules that safely modulate pliancy genes.
AI-driven mapping of pliancy networks to tailor individual treatments.
Collaboration between academia and industry to launch early clinical trials.

References

Sato, Y., Mei, X., et al. (2025). Latent epigenetic programs in Müller glia contribute to stress, injury, and disease response in the retina. Developmental Cell, 60(4), 621–640. Link
St. Jude Children’s Research Hospital (2025). Discovery of pliancy genes showcases role of latent epigenetic programs in retinal recovery. Link