Project: Photoporation of the inner limiting membrane to enhance retinal drug delivery after intravitreal injection

2018-10-01 – 2022-09-30

Abstract

Intravitreal injection, injection in the gel of the eyeball, is a commonly applied method in the clinic
for delivery of drugs (e.g. antibodies) to the retina. However, larger structures like gene carriers
more than often do not reach the retina. This is unfortunate since many blinding diseases require
delivery to this target site. It has been shown that the inner limiting membrane (ILM), a thin
membrane between the vitreous gel and the retina, is the primary barrier hindering effective drug
delivery to the retina via intravitreal injection. To overcome this barrier we propose to apply
photoporation to perforate the ILM resulting in the creation of entryways for drug carriers to enter
the retina. Here, gold nanoparticles (AuNPs) are injected and allowed to accumulate at the ILM
followed by treatment with an extremely short laser pulse. This laser energy heats up the AuNP
forming vapour bubbles that upon collapse damage their surroundings – in our case the ILM. In
this project, we aim to provide proof-of-concept of this innovative approach by testing it on an inhouse
developed ex vivo bovine retinal explant. We will furthermore examine the safety of the
different factors of the approach (the laser, the AuNPs) in this model, as well as the potential
toxicity of AuNP in vivo in mice.