New study: mineralocorticoid receptor antagonism improves corneal integrity in a rat model of limbal stem cell deficiency

Mineralocorticoid receptor antagonism improves corneal integrity in a rat model of limbal stem cell deficiency

The clear front part of the eye, called the cornea, helps us see by focusing light. This part of the eye stays healthy thanks to special cells called limbal stem cells. When these cells are damaged or lost—due to injury, disease, or certain treatments—it leads to a condition called limbal stem cell deficiency (LSCD). This can cause clouding of the cornea, pain, and severe vision problems.

Currently, treatment options for LSCD and other rare eye diseases are limited and not always easy to access. That’s why the Restore Vision project is working to find new treatments that could help improve the lives of patients with these diseases, by developing new formulations and eye drops, as well as repurposing existing drugs.

What was the purpose of this study?

In this study, our team at INSERM, explored whether a group of medications called mineralocorticoid receptor antagonists (MRAs)—originally used to treat heart and kidney conditions—could help heal and protect the cornea in LSCD.

Using a well-established rat model that mimics the eye damage seen in human LSCD, the researchers tested two types of MRAs and studied their effects on corneal healing over two weeks.

What were the main findings?

Using a combination of in vivo imaging and histological analyses researchers evaluated the treatment effects and saw that MRAs:

– Reduced swelling, abnormal blood vessel growth, and inflammation in the cornea

– Improved the structure and clarity of the cornea, helping it heal better

– Supported the growth of corneal nerves, which are important for eye health and comfort

– Activated genes linked to repair and stem cell support, while turning off harmful ones related to scarring and inflammation

In another part of the study, rats with an overactive version of the MR pathway showed worse eye problems—confirming that blocking this pathway can be helpful.

What are the main implications?

These findings support the idea that MRAs—already used safely for other health conditions—might be repurposed to treat LSCD. This approach could speed up the development of novel treatments for rare ocular diseases, making Restore Vision one step closer of accessible, effective treatments.

However, one limitation of the current study is the short duration of the LSCD model used, which may not fully represent the long-term progression of the disease in humans. Although the model is widely accepted in preclinical research, future studies will need to assess the longer-term effects of MRA treatment. Additionally, because the treatment in this study was delivered systemically, further research is required to determine whether similar benefits can be achieved with topical application via eye drops—the preferred route in clinic.

What are the next steps?

Building on the results of this study, the research team is now shifting focus to testing a newly developed eye drop formulation of the MRA compound SPL. This formulation has already shown excellent tolerance in rat models (Daniela Rodrigues-Braz et al., 2023), and the next step is to confirm its effectiveness in delivering the drug to the eye surface. This will help establish whether the therapeutic benefits observed with systemic treatment can be replicated with topical use.

Before moving to clinical translation, full preclinical development will also be conducted. This includes regulatory toxicity testing, pharmacokinetic profiling, the production of medical-grade compounds, and completing all necessary regulatory assessments. These steps are essential to test the safety, effectiveness, and scalability of any treatment before it can move into human trials and ultimately become available to patients.

Read the full study 👉https://www.sciencedirect.com/science/article/pii/S0753332225001738?via%3Dihub