Effects of Ultrasound Contrast Agent-Mediated Nerve Growth Factor on Apoptosis of Retinal Ganglion Cells in Mice with Glaucoma.

ABSTRACT

With an increasing incidence in recent years, glaucoma (GL) has gradually become a global public health problem for humans of all ages. Nerve growth factor (NGF) eye drops, with well-documented stable effect in the treatment of GL, can be potentiated by the administration of NGF drugs via ultrasound contrast agent (UCA). This study analyzed the efficacy of NGF+UCA on GL mice and the influencing mechanism on retinal ganglion cells and further explored the pathological changes of GL mice under different UCA irradiation duration. In this study, we established GL mouse models and treated the mouse with NGF+UCA. The effect of NGF+UCA on intraocular pressure in mice was observed; the flash visual evoked potential of mice was compared; the changes of retinal structure, inflammation index, and oxidative stress index were observed, and autophagic protein levels were tested. Finally, the influence of UCA irradiation duration on GL symptoms was observed. The results showed that the intraocular pressure of mice decreased greatly, while their flash visual evoked potential and nervous layer of retina increased, and their ganglion cells showed stronger proliferation activity and weaker apoptosis and autophagy, indicating that UCA-mediated NGF can strongly improve the pathological condition of GL mice. In addition, PI3K/AKT pathway-associated proteins were inhibited in retina under the intervention of NGF+UCA, which further suggests that the influence of UCA-mediated NGF on GL is achieved by inhibiting autophagy of retinal ganglion cells and enhancing their apoptosis via the PI3K/AKT signaling pathway. Moreover, we found that in the treatment of GL, three weeks of UCA irradiation and six weeks caused no significant difference in the pathological manifestations and ganglion cells of mice, while after six weeks of irradiation, the level of NLRP3 in mice increased. In conclusion, UCA-mediated NGF can significantly improve the pathological condition of GL mice and improve the apoptosis of retinal ganglion cells by inhibiting autophagy, which is associated with the inhibition of the PI3K/AKT signal pathway. In terms of selection of UCA irradiation duration, three weeks of irradiation is enough to yield good clinical results.