Advances in Corneal Healing Research Drive New Treatments for Rare Eye Diseases

Rare eye diseases are a major cause of untreatable blindness in Europe, affecting individuals of all ages. The RESTORE VISION project, led by Juana Gallar, a professor at UMH and head of the Ocular Neurobiology Laboratory at the Institute for Neurosciences (IN), aims to develop new and accessible treatments by restoring the immune, vascular, and nervous systems of the ocular surface.

Targeted Rare Eye Diseases

The RESTORE VISION team has identified seven rare ocular diseases that primarily affect the cornea and ocular surface:

Aniridia: A Complex Genetic Disorder

       • Aniridia, affecting 1 in 80,000 people, is characterized by partial or complete absence of the iris.

       • It is mainly caused by a PAX6 gene mutation, disrupting eye development during gestation.

       • Symptoms include photophobia, glare sensitivity, and potential blindness, alongside cataracts, glaucoma, and corneal abnormalities.

       • Current treatments focus on early visual stimulation, special lenses to manage photophobia, and in some cases, artificial iris implants.

       • “Aniridia cannot be prevented, so our efforts are directed toward developing affordable solutions to enhance patients’ quality of life,” said M. Carmen Acosta, a UMH professor and RESTORE VISION researcher.

Other Rare Eye Diseases Under Study

Besides aniridia, RESTORE VISION is investigating six additional rare diseases affecting the corneal surface:

       1. Neurotrophic Keratopathy (NK): A degenerative disease causing corneal nerve damage, leading to loss of corneal sensation.

       2. Ocular Cicatricial Pemphigoid: A rare autoimmune disease affecting mucous membranes, including the ocular surface.

       3. Ectrodactyly-Ectodermal Dysplasia-Clefting (EEC) Syndrome: A genetic disorder associated with malformed tear ducts, photophobia, and corneal ulcers.

       4. Graft-Versus-Host Disease (GVHD): A post-transplant complication that frequently leads to severe dry eye disease.

       5. Limbal Stem Cell Deficiency (LSCD): Prevents corneal epithelium renewal, leading to irreversible corneal damage.

       6. Corneal Neovascularization: Abnormal blood vessel growth in the cornea, causing inflammation and vision loss.

Key Research Findings: Understanding Corneal Sensory Neurons

Recent research from the Ocular Neurobiology Laboratory has provided significant insights into corneal nerve function, which could be crucial for developing treatments.

Role of Cold-Sensitive Trigeminal Neurons

A study published in Acta Ophthalmologica identified two subpopulations of cold-sensitive trigeminal neurons responsible for detecting temperature changes on the corneal surface. These neurons help regulate spontaneous blinking and baseline tear production, both of which are essential for corneal health.

“Understanding how these neurons function is critical to assessing their role in conditions that impair corneal sensitivity, such as neurotrophic keratopathy. This knowledge could contribute to designing treatments aimed at restoring nerve function in rare eye diseases,” explained Ariadna Díaz Tahoces, lead author of the study.

Innovative Corneal Nerve Regeneration Model

The research team has developed a novel method to study corneal nerve regeneration using laser-induced lesions in the corneal nerve fibers of adult mice.

       • In mice lacking the SARM1 protein—which regulates nerve degeneration—nerves deteriorated more slowly, but their regenerative capacity was also affected.

       • This live-mammal model provides a new approach to studying nerve repair in rare corneal diseases, potentially leading to new therapeutic solutions.

"This model allows us to analyze how nerves recover after injury and could help us understand nerve dysfunction in rare diseases affecting corneal innervation," said Almudena Íñigo Portugués, lead author of the study.

Next Steps: Developing and Testing New Therapies

The RESTORE VISION project is advancing towards clinical applications, focusing on:

       • New drug formulations for rare ocular diseases.

       • Repurposing existing medications for corneal regeneration.

       • Finalizing clinical documentation for submission to ethics committees and regulatory authorities.

The Institute for Neurosciences UMH-CSIC will play a pivotal role in evaluating topical therapies for corneal healing.

“Our work focuses on identifying therapeutic targets in cells and conducting preclinical studies before transitioning to clinical trials,” said Gallar.

Once validated, the RESTORE VISION consortium will establish clinical protocols and develop legislative recommendations to accelerate patient access to these innovative treatments.

Reference:

Ariadna Diaz‐Tahoces et al, Characterization of cold thermosensitive trigeminal neurons that innervate the cornea, Acta Ophthalmologica (2025). DOI: 10.1111/aos.17247