Pulsed Laser Light and Nano-encapsulated Ocular Dyes for Advanced Therapies in the Eye

Introduction

Ocular diseases affect the quality of life of millions of patients. Despite improvements in pharmacological treatments, the arsenal of medications to treat severe ocular diseases today remains rather restricted to traditional drugs.

Need for Novel Administration Methods

The use of most modern biotherapeutics like proteins and nucleic acids could be a major step forward. However, current ways of administration such as eye drops and intravitreal injections are no longer sufficient to deliver these drugs to most targets in the eye. Therefore, novel concepts allowing biotherapeutics to safely overcome ocular barriers are of high interest.

Safety Concerns in Ocular Surgery

In ocular surgery, pulsed-lasers (P-Ls) are used for ‘tissue cutting’, though safety concerns remain. DYE-LIGHT hypothesizes that strategies which would allow the use of P-Ls in the eye at much lower energy than today could considerably improve safety and pave the way for both novel ocular therapies and advanced surgical interventions.

Exploration of Vital Dyes

DYE-LIGHT will explore vital dyes, as used by ocular surgeons to stain tissues, as photosensitizers. DYE-LIGHT follows the recent observation that P-L irradiation of ocular dyes can result in the formation of water vapor nanobubbles (‘dye-based nanobubbles’) and thermophoretic transport (‘dye-based thermophoresis’).

Energy Efficiency

Interestingly, these biophysical phenomena occur at a laser energy that is ~ 1000 times less than a P-L alone. As compared to free dyes, dyes encapsulated in nanocarriers are expected to penetrate less into the retina, which might improve safety.

Focus on Nano-Encapsulated Dyes

Therefore, the focus in DYE-LIGHT will be on nano-encapsulated ocular dyes. DYE-LIGHT will explore the potential of dye-based nanobubbles for:

1. Delivery of nucleic acids in the corneal endothelium
2. Spatial selective vitreolysis in the eye

Controlled Transport of Nanomedicines

Finally, DYE-LIGHT will explore dye-based thermophoresis for controlled transport of nanomedicines injected in the vitreous towards the retina. If successful, this might open new perspectives to improve the efficacy of retinal drug and gene delivery.