Neuroprotective Effects of Human Adipose-Derived Mesenchymal Stem Cells in Oxygen-Induced Retinopathy.

This study was designed to provide evidence of the neuroprotective of human adipose-derived mesenchymal stem cells (hADSCs) in oxygen-induced retinopathy (OIR). In vivo, hADSCs were intravitreally injected into OIR mice. Various assessments, including HE (histological evaluation), TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining, electroretinogram (ERG) analysis, and retinal flat-mount examination, were performed separately at postnatal days 15 (P15) and 17 (P17) to evaluate neurological damage and functional changes. Western blot analysis of ciliary neurotrophic factor (CNTF), glial cell line-derived neurotrophic factor (GDNF), and brain-derived neurotrophic factor (BDNF) was conducted at P17 to elucidate the neuroprotective mechanism. The P17 OIR group exhibited a significant increase in vascular endothelial cell nuclei and neovascularization that breached the ILM (inner limiting membrane) to the P17 control group. In addition, the retinal nonperfusion areas in the P17 OIR group and the number of apoptotic retinal cells in the P15 OIR group were significantly higher than in the corresponding hADSCs treatment group and control group. There was no significant thickness change in the inner nuclear layer (INL) but the outer nuclear layer (ONL) in the P17 OIR treatment group compared with the P17 OIR group. The cell density in the INL and ONL at P17 in the hADSCs treatment group was not significantly different from the OIR group. The amplitude of a-wave and b-wave in scotopic ERG analysis for the P17 OIR group was significantly lower than in the P17 hADSCs treatment group and the P17 control group. Furthermore, the latency of the a-wave and b-wave in the P17 OIR group was significantly longer than in the P17 hADSCs treatment group and the P17 control group. In addition, the expression levels of CNTF and BDNF in the P17 OIR group were statistically higher than those in the P17 control group, whereas the expression of GDNF was statistically lower in the P17 OIR group, compared with the P17 control group. The expression of CNTF and GDNF in the P17 hADSCs treatment group was statistically higher than in the P17 OIR group. However, the expression of BDNF in the P17 hADSCs treatment group was statistically lower than in the P17 OIR group. This study provides evidence for the neuroprotective effects of hADSCs in OIR.

Expression of the neuroprotective factors BDNF, CNTF, and FGF-2 in normal and oxygen induced retinopathy.

Introduction: Oxygen-induced retinopathy is a type of retinal pathological neovascularization (NV) disease that leads to vision loss and translates to a significant societal cost. Anti-vascular endothelial growth factor (VEGF) and anti-inflammatory treatments have been widely used in the clinic, but the results have not been entirely satisfactory. It is necessary to explore other treatments for Ischemic retinal diseases. Methods: The oxygen-induced retinopathy (OIR) model was induced from P7 to P12 as described. Histology evaluation (HE) and retina flat mounts were checked at P17 to confirm the establishment of the OIR model. Retinal ganglion cell (RGC) degeneration was checked by transmission electron microscopy at P17 to confirm the neurological damage caused by OIR. Western blot analysis was performed at P12, P15, and P17 to study the expression of brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and fibroblast growth factor 2 (FGF-2) in normal and OIR mice. Comparative analysis of the expressions of BDNF, CNTF, and FGF-2 in normal and OIR mice was performed. Results: There were many retinal NV and non-perfusion areas in OIR P17. RGCs were degenerated at OIR P17. The expressions of BDNF, CNTF, and FGF-2 gradually increased from P12 to P17 in normal mice and were much higher in OIR mice. The expression curves of BDNF, CNTF, and FGF-2 in the OIR model were inconsistent and did not correlate with each other. Discussion: This study provides evidence for changes in BDNF, CNTF, and FGF-2 in Oxygen-induced retinopathy.