Work

Retinal neuroprotection and microglia M1/M2 polarization modulation of triamcinolone acetonide and basic fibroblast growth factor co-delivered in liposomes after optic nerve injury

Year: 2026

Type: article

Abstract: Optic nerve diseases can result in the degeneration of retinal ganglion cells (RGCs) and their axons, ultimately causing irreversible blindness. Current conventional treatments are limited by inconsistent efficacy, adverse effects or poor tolerability, underscoring the urgent need for more effective therapeutic approaches. Triamcinolone acetonide (TA) and basic fibroblast growth factor (bFGF) have been identified as neuroprotective agents; however, investigations into their combined effects remain scarce. The present study describes a PEG-modified liposome co-encapsulating TA and bFGF, administered via intravitreal injection in a murine model of optic nerve crush (ONC). This co-delivery system demonstrates superior effects in protecting RGCs, promoting axonal regeneration, and modulating microglia M1/M2 shift compared to the monotherapies. RNA sequencing analysis and molecular experiments revealed that TA/bFGF@Lipo was involved in the NF-κB/p65 signaling pathway and PI3K/AKT signaling pathway. Notably, the expression of tissue inhibitors of metalloproteinases-1 (TIMP1) was significantly upregulated following the liposomes treatment and exhibited a strong correlation with the expression of microglia M2 biomarkers. Subsequent experiments demonstrated that rmTIMP1 promoted BV2 microglia M1/M2 shift in a dose-dependent manner, and TIMP1 knockdown significantly decreased the RGCs survival and M2 polarization of retinal microglia induced by TA/bFGF@Lipo. Collectively, this research establishes TA/bFGF@Lipo as an effective therapeutic strategy for optic nerve injury, and highlights the essential role of TIMP1 in RGCs protection and microglia M2 polarization, offering novel insights for the treatment of optic nerve diseases.

Source: Materials Today Bio

DOI: 10.1016/j.mtbio.2026.103816