# Limbal Epithelial Stem Cells in Review: Immune and Lymphangiogenic Privilege and Their Clinical Relevance

## TL;DR

Limbal epithelial stem cells help keep the cornea clear by controlling immune and blood vessel responses, and their dysfunction can lead to vision loss.

## Contribution

The paper identifies ABCB5 as a key marker for limbal stem cells and highlights their role in maintaining corneal immune and vascular balance.

## Key findings

- LESCs regulate corneal immune and lymphangiogenic privilege by integrating biochemical and mechanical signals.
- ABCB5+ epithelial cells are crucial for repair, remodelling, and immune suppression in the limbal niche.
- Disruption of the limbal niche leads to limbal stem cell deficiency, inflammation, and vision loss.

## Abstract

What are the main findings?
Limbal epithelial stem cells (LESCs) are central regulators of corneal immune and (lymph)angiogenic privilege, integrating niche-derived biochemical and mechanical cues to balance regeneration with avascularity.There are key stem cell markers that identify functionally distinct limbal cell subsets, with specialised epithelial cells supporting repair-associated angiogenic responses and matching stromal cells exerting strong anti-inflammatory and anti-(lymph)angiogenic effects.

Limbal epithelial stem cells (LESCs) are central regulators of corneal immune and (lymph)angiogenic privilege, integrating niche-derived biochemical and mechanical cues to balance regeneration with avascularity.

There are key stem cell markers that identify functionally distinct limbal cell subsets, with specialised epithelial cells supporting repair-associated angiogenic responses and matching stromal cells exerting strong anti-inflammatory and anti-(lymph)angiogenic effects.

What are the implications of the main findings?
Loss or dysfunction of the limbal niche disrupts immune and vascular privilege, driving limbal stem cell deficiency (LSCD), chronic inflammation, neovascularization, and vision loss.Future LSCD therapies should combine epithelial regeneration with stabilization of immune and vascular privilege, leveraging stem cell populations or their paracrine signals to achieve durable ocular surface restoration.

Loss or dysfunction of the limbal niche disrupts immune and vascular privilege, driving limbal stem cell deficiency (LSCD), chronic inflammation, neovascularization, and vision loss.

Future LSCD therapies should combine epithelial regeneration with stabilization of immune and vascular privilege, leveraging stem cell populations or their paracrine signals to achieve durable ocular surface restoration.

The cornea maintains transparency by preserving immune and (lymph)angiogenic privilege through active suppression of inflammation and vascular invasion, a process centrally regulated by limbal epithelial stem cells (LESCs) located at the corneoscleral junction. Beyond renewing the corneal epithelium, LESCs maintain immune and vascular balance via extracellular matrix interactions and paracrine signalling, exerting predominantly anti-inflammatory and anti-(lymph)angiogenic effects in vivo. Disruption of the limbal niche by trauma, UV exposure, or genetic disorders such as aniridia leads to limbal stem cell deficiency (LSCD), chronic inflammation, loss of corneal avascularity, and vision loss. The identification of ABCB5 as a key LESC marker has clarified functional limbal subsets, highlighting ABCB5+ epithelial cells as mediators of repair, remodelling, and immune suppression, and positioning them as promising therapeutic targets for treatments that restore both epithelial integrity and corneal immune privilege.