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.
Highlights
Glaucoma (GL), as an ophthalmic disease with fast onset and great harm in clinic, is very common among the middle-aged and elderly [1]
The intraocular pressure (IOP) was not statistically different between the Nerve growth factor (NGF)+ultrasound contrast agent (UCA) group and the control group (P > 0:05), which was lower than that of the NGF group and model group, and the IOP was higher in the model group compared with the NGF group (P < 0:05)
The latency of P100 wave was the lowest in the control group and the highest in the model group, and the NGF+UCA group showed a lower latency of P100 wave compared with the NGF group (P < 0:05)
Summary
Glaucoma (GL), as an ophthalmic disease with fast onset and great harm in clinic, is very common among the middle-aged and elderly [1]. There are approximately 900,000 new cases with GL worldwide each year, with an emerging trend of the disease at younger ages [2]. GL is mainly induced by the imbalance of intraocular pressure (IOP), which has serious damage to various parts of the eyeball [4]. It is usually pathologically manifested as optic atrophy and vision loss, and over 70% of patients with GL have gone blind due to improper or untimely treatment [5]. It is estimated that by 2030, the Computational and Mathematical Methods in Medicine number of GL-related blindness could exceed 20 million worldwide [6]
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