The Safety and Protective Effects of Intravitreal Injection of Human Adipose-Derived Mesenchymal Stem Cells in a Rat Model of Retinal Ischemia/Reperfusion Injury

Abstract

Purpose: The purpose of this study was to evaluate the safety and protective effects of intravitreal injection of human adipose-derived mesenchymal stem cells (ADMSCs) in a rat model of retinal ischemia/reperfusion (I/R) injury induced by anterior chamber perfusion.

Methods: Two weeks after induction of I/R injury, rats received a single intravitreal injection of human ADMSCs at doses of 2×10⁴ cells or 5×10⁴ cells suspended in 3 μL saline. Control rats received 3 μL saline or no injection. Retinal and optic nerve changes were assessed at two weeks after injection using immunofluorescence, hematoxylin and eosin staining, toluidine blue staining, and polymerase chain reaction to evaluate inflammation-related and neurotrophic factors.

Results: Intravitreal injection of human ADMSCs significantly reduced the number of apoptotic retinal ganglion cells after I/R injury, preserved the ganglion cell layer, and increased expression of neurotrophic factors such as brain-derived neurotrophic factor and insulin-like growth factor 1. The high-dose group (receiving 5×10⁴ cells) demonstrated superior neuroprotective effects compared to the low-dose group (receiving 2×10⁴ cells) as evidenced by less retinal ganglion cell apoptosis. In addition, histopathological analysis revealed localized tissue remodeling and increased microglial infiltration, particularly in the low-dose group.

Conclusion: The safety of intravitreal human adipose-derived mesenchymal stem cell transplantation requires further investigation, particularly with regard to potential proliferative responses and their long-term effects. In addition, the optimal dosage of adipose-derived mesenchymal stem cells needs to be explored to balance therapeutic efficacy and minimize adverse outcomes. which was associated with structural retinal damage. In addition, the high-dose group exhibited a potential risk of inflammation or maladaptive changes.