Reactivating Intrinsic Recovery Mechanisms of Retinal Ganglion Cells for Neuroprotection and Precision Therapy in Glaucoma

Onderzoeker: Wenting You

Title: Reactivating Intrinsic Recovery Mechanisms of Retinal Ganglion Cells for Neuroprotection and Precision Therapy in Glaucoma

Project description: My research aims to develop novel neuroprotective strategies for glaucoma by harnessing the intrinsic recovery capacity of dying retinal ganglion cells (RGCs).

The irreversible step in glaucoma pathology is the death of RGCs. Our previous work demonstrated that dying RGCs possess an unexpected ability to halt the process of regulated cell death and recover from various apoptotic injuries to a healthy state, with PGC-1α identified as a key regulator of this recovery process. Given the limited regenerative capacity of RGCs, enhancing this intrinsic recovery capacity could be a promising therapeutic strategy for glaucoma.

Building on these findings, our current research utilizes human embryonic stem cell-derived RGCs and retinal organoids to elucidate the molecular mechanisms that enable neuronal recovery, and to explore whether similar mechanisms may be exploited to protect other non-regenerating cells, such as cardiomyocytes. In parallel, we combine in silico molecular docking with high-throughput screening of compound libraries to identify novel PGC-1α activators capable of promoting RGC survival and repair.

In addition, we are generating patient-specific induced pluripotent stem cell (iPSC)-derived RGC models from glaucoma patients to investigate inter-individual variability in neuronal recovery capacity. These personalized models will also serve as a platform for testing candidate compounds, laying the groundwork for mechanism-based, patient-tailored neuroprotective interventions