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

The Ocular Neurobiology laboratory at the Institute for Neurosciences, a joint center of Miguel Hernández University (UMH) in Elche and the Spanish National Research Council (CSIC), is participating in the European project RESTORE VISION, an ambitious initiative aimed at developing new treatments for rare eye diseases such as aniridia and neurotrophic keratopathy. With €8 million in funding from the European Commission, this consortium brings together six research institutions, three SMEs, and patient associations with a common goal: to improve eye health and quality of life for those affected by these conditions. This laboratory has described the activity of key neurons involved in corneal sensitivity and has developed an experimental model to study nerve regeneration in the cornea, advances that could contribute to the study and development of treatments for rare eye diseases.

Rare eye diseases are the leading cause of untreatable blindness in Europe and affect people of all ages. The RESTORE VISION scientific team has identified seven rare ocular conditions that impact the cornea and the rest of the ocular surface. "With a comprehensive approach, we aim to restore the normal function of the immune, vascular, and nervous systems of the ocular surface by studying existing drugs while also developing new, accessible treatments," says Juana Gallar, a professor at UMH who leads the project and the Ocular Neurobiology Laboratory at the IN.

Among these seven rare diseases is aniridia, which affects one in every 80,000 people and is characterized by the partial or complete absence of the iris. In most cases, it results from a mutation in the PAX6 gene, preventing proper eye development during gestation. In addition to photophobia and glare sensitivity, aniridia can lead to blindness and other complications such as cataracts, glaucoma, or corneal abnormalities. "Aniridia means 'lack of iris', but it is actually a disease that affects multiple parts of the eye", explains Mª Carmen Acosta, a professor at UMH and a researcher in the project.

Currently, there is no cure for aniridia, and existing treatments only address specific symptoms. Early intervention is crucial, with a focus on visual stimulation during childhood. Later, special lenses help reduce photophobia and glare, while in some cases of partial aniridia, surgical implants of artificial irises may be used. "Unfortunately, aniridia cannot be prevented, so efforts are focused on developing affordable solutions to improve patients' quality of life," Acosta concludes.

In addition to aniridia and neurotrophic keratopathy, RESTORE VISION is studying five other rare diseases affecting the ocular surface: ocular cicatricial pemphigoid, an autoimmune disease that affects the mucous membranes of the mouth and the eye's surface; ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome, which often involves malformations of the tear ducts, along with photophobia and corneal ulcers; graft-versus-host disease (GVHD), a complication of allogeneic transplants that manifests in the eyes, often causing dry eye disease; limbal stem cell deficiency (LSCD), which prevents the renewal of the corneal epithelium, eventually leading to incurable corneal damage; and corneal neovascularization, a process in which blood vessels develop abnormally in the cornea, which is normally avascular, leading to inflammation and vision loss.

Recent research from this laboratory is providing key insights that could be crucial for the RESTORE VISION project. In a study published in Acta Ophthalmologica, researchers have described the characteristics of two subpopulations of cold-sensitive trigeminal neurons that innervate the cornea. These neurons, classified as high and low basal activity, play a crucial role in detecting temperature changes on the eye's surface and may be involved in regulating spontaneous blinking as well as baseline tear production. "Understanding how these neurons function is essential to determine how they are affected in diseases that impair corneal sensitivity, such as neurotrophic keratopathy. This knowledge could help design treatments aimed at restoring nerve function in patients with rare eye diseases", explains Ariadna Díaz Tahoces, lead author of the publication.

On the other hand, the Ocular Neurobiology laboratory has developed a new method to study nerve regeneration in the cornea. Using a laser, they have been able to create small, controlled lesions in the corneal nerve fibers of adult mice to then analyze their regeneration. In their experiments, they discovered that in mice lacking the SARM1 protein, responsible for nerve degeneration after injury, nerves take longer to deteriorate, but their regenerative capacity is also affected. "This model allows us to study, in living mammals, how nerves recover after an injury and could contribute to understanding what happens in rare diseases that affect corneal innervation, ultimately aiding in the development of new treatments", explains Almudena Íñigo Portugués, lead author of the study.

The RESTORE VISION project is making progress in developing new drug formulations and identifying existing medications that could be used to treat rare eye diseases. Clinical documents are currently being finalized for submission to ethics committees and regulatory authorities, bringing the project closer to the possibility of treating the first patients with rare ocular diseases using RESTORE VISION therapies.

The Institute for Neurosciences UMH-CSIC will play a crucial role in evaluating topical therapies for corneal regeneration. "Our work focuses on identifying therapeutic targets in cells and conducting preclinical studies before moving on to clinical trials", explains Juana Gallar. Once the treatments are validated, the consortium will establish clinical protocols and formulate legislative recommendations to accelerate access to these medical innovations.

With RESTORE VISION, the scientific, medical, and business communities come together in a collective effort to transform the treatment of rare eye diseases and ensure that medical advances reach those who need them most. This project is funded with €8 million from the European Commission through the Horizon Europe program and is also supported by various research institutions and companies specialized in ophthalmology.

More information:
Diaz‐Tahoces, A., Aleixandre‐Carrera, F., Velasco, E., Acosta, M. C., & Gallar, J. (2025). Characterization of cold thermosensitive trigeminal neurons that innervate the cornea. Acta Ophthalmologica, 103.

Provided by Miguel Hernandez University of Elche