Injectable corneal endothelial cell therapy: recent progress, translational barriers, and future directions

Area of Science:

• Ophthalmology
• Regenerative Medicine
• Cell Therapy

Background:

• Corneal endothelial dysfunction, often from Fuchs endothelial corneal dystrophy or pseudophakic bullous keratopathy, causes vision loss when endothelial cell density decreases.
• Current treatments like Descemet stripping automated endothelial keratoplasty and Descemet membrane endothelial keratoplasty face challenges including donor scarcity and immune rejection.

Purpose of the Study:

• To review recent advancements in injectable corneal endothelial cell (CEC) therapy.
• To critically evaluate the translational challenges of this regenerative approach.
• To discuss future directions for establishing CEC injection as a global treatment.

Main Methods:

• A narrative review of pre-clinical and clinical studies on CEC injection therapy.
• Analysis of literature on Human corneal endothelial cells (HCEC) preparation, culture, delivery methods, and cell survival strategies.
• Inclusion of studies on preclinical models and human clinical trials to assess safety and efficacy.

Main Results:

• Injectable CEC therapy has advanced, with ROCK inhibitors improving corneal transparency in conjunction with cultured CECs.
• Novel delivery techniques such as hydrogels and magnetically guided injections show promise in preclinical studies.
• Challenges remain in maintaining cell phenotypic stability and ensuring long-term safety and efficacy in human trials.

Conclusions:

• Injectable CEC therapy presents a minimally invasive alternative to corneal transplantation for endothelial failure.
• Encouraging early clinical outcomes necessitate further optimization of cell preparation and delivery.
• Establishing this therapy as a scalable, globally applicable treatment requires addressing long-term safety and efficacy concerns.