ILM photodisruption: a biophotonic approach to promote retinal ganglion cell engraftment as a cure for blindness

01 November 2023 → 31 October 2026
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • In vitro testing
    • Non-clinical studies
    • Biopharmaceutics
    • Ophtalmology
cell delivery barriers stem cell delivery to the retina pulsed laser technology
Project description

Glaucoma is a leading cause of irreversible blindness worldwide. Its primary hallmark is the progressive loss of retinal ganglion cells (RGCs) which inevitably results in vision loss. A revolutionary cure could be the replacement of lost neurons by transplantation of stem-cell derived RGCs. Surely, earlier studies prove that RGC replacement is a feasible and promising concept. A primary obstacle, however, is the poor migration of the intravitreally injected cells into the retina due to their accumulation at the inner limiting membrane (ILM). In this project I therefore aim to significantly promote RGC transplantation by local disruption of the ILM using a light-based approach I developed over the last 3 years. In this approach, the photothermal dye indocyanine green (ICG) is delivered to the ILM and irradiated with extremely short laser pulses resulting in the creation of vapor nanobubbles which upon their collapse locally disrupt the ILM. Specifically, one work package is dedicated to the detailed assessment of the in vivo efficacy and tolerance toward ILM photodisruption. In a second work package we will maximally employ the tunability of our approach by examining ILM integrity upon treatment with several laser scanning patterns in combination with varying ICG concentrations and laser fluences. Finally, the impact of these treatment modules on the retinal integration of iPSC-RGCs will be investigated based on co-culture of the donor RGCs on bovine organotypic explants.