A minimally invasive therapy could redefine vision preservation in inherited retinal diseases

Retinitis pigmentosa (RP) affects approximately 1 in 4,000 people worldwide and remains one of the most devastating inherited causes of blindness. Characterized by progressive death of photoreceptor cells, RP currently has no universal cure. But new research suggests that a simple eye drop might one day dramatically change this outlook.

A March 2025 study published in Communications Medicine by Dr. Alexandra Bernardo-Colón and colleagues introduces H105A, a small peptide derived from pigment epithelium-derived factor (PEDF), as a promising neuroprotective therapy. Delivered via eye drops, H105A targets photoreceptor cells and delays their degeneration in both murine models and human retinal organoids.

A Game-Changer in RP Treatment

What sets H105A apart is its mode of action and delivery. Unlike gene therapy or surgical implants, this approach is non-invasive, scalable, and potentially gene-agnostic. By binding to PEDF-R, a known neuroprotective receptor in retinal tissue, the H105A peptide stimulates survival pathways and suppresses apoptosis.

In two distinct RP mouse models—rd10 and RhoP23H/+—daily administration of H105A or its parent 17-mer peptide via eye drops not only preserved photoreceptor structure but also improved retinal function, as confirmed through electroretinography (ERG). In the more aggressive rd10/Serpinf1-/- variant (lacking endogenous PEDF), results were also significant.

Critically, H105A’s benefits extended beyond animal studies. In human stem cell-derived retinal organoids subjected to oxidative stress (mimicking disease progression), H105A significantly reduced photoreceptor death, highlighting its potential in human applications.

Lasting Impact Through Gene Therapy

For long-term delivery, the team also developed an adeno-associated virus (AAV) gene therapy version of H105A. A single injection into the eye of RhoP23H/+ mice delayed degeneration and sustained retinal function for up to six months—a striking outcome that supports future clinical translation.

Notably, this gene therapy was delivered via intravitreal injection, which is safer and more broadly effective than subretinal methods traditionally used in retinal disorders.

Why This Matters

RP’s genetic heterogeneity has long complicated treatment development. The H105A peptide, however, bypasses the need to tailor therapies to individual mutations. It works on universal cellular pathways, offering a rare, mutation-independent avenue for therapy.

Moreover, topical administration as eye drops would dramatically reduce patient burden and cost, while potentially making early intervention feasible on a wide scale. This aligns with a broader trend in ophthalmology: developing less invasive, patient-friendly treatments for previously intractable diseases.

What’s Next?

The study authors emphasize the need for further testing to confirm efficacy, optimize dosing, and assess safety in human trials. Still, the foundation laid by this research is compelling. H105A and similar PEDF-derived peptides could soon offer real therapeutic benefit—not just to those with RP, but potentially in age-related macular degeneration, diabetic retinopathy, and other photoreceptor-related conditions.

As the field moves toward more accessible, gene-agnostic treatments, peptide-based eye drops may well become a mainstay in vision-preserving medicine.

Source:
Alexandra Bernardo-Colón, Andrea Bighinati, Shama Parween, et al. “H105A peptide eye drops promote photoreceptor survival in murine and human models of retinal degeneration.” Communications Medicine (2025). https://doi.org/10.1038/s43856-025-00381-1