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

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Yan Ke ◽  
Lina Huang ◽  
Bingheng Chen ◽  
Jing Sima ◽  
Jiaguo Cao ◽  
...  

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.

Author(s):  
C. Ross Ethier ◽  
Richie Abel ◽  
E. A. Sander ◽  
John G. Flanagan ◽  
Michael Girard

Glaucoma describes a group of potentially blinding ocular disorders, afflicting c. 60 million people worldwide. Of these, c. 8 million are bilaterally blind, estimated to increase to 11 million by 2020. The central event in glaucoma is slow and irreversible damage of retinal ganglion cells, responsible for carrying visual information from the retina to the brain (Figure 1). Intraocular pressure (IOP) is a risk factor for glaucoma1–4, and significant, sustained IOP reduction is unequivocally beneficial in the clinical management of glaucoma patients2, 3, 5. Unfortunately, we do not understand how elevated IOP leads to the loss of retinal ganglion cells.


2021 ◽  
Author(s):  
Sophie Pilkinton ◽  
T.J. Hollingsworth ◽  
Brian Jerkins ◽  
Monica M. Jablonski

Glaucoma is a multifactorial, polygenetic disease with a shared outcome of loss of retinal ganglion cells and their axons, which ultimately results in blindness. The most common risk factor of this disease is elevated intraocular pressure (IOP), although many glaucoma patients have IOPs within the normal physiological range. Throughout disease progression, glial cells in the optic nerve head respond to glaucomatous changes, resulting in glial scar formation as a reaction to injury. This chapter overviews glaucoma as it affects humans and the quest to generate animal models of glaucoma so that we can better understand the pathophysiology of this disease and develop targeted therapies to slow or reverse glaucomatous damage. This chapter then reviews treatment modalities of glaucoma. Revealed herein is the lack of non-IOP-related modalities in the treatment of glaucoma. This finding supports the use of animal models in understanding the development of glaucoma pathophysiology and treatments.


2015 ◽  
Vol 117 ◽  
pp. 136
Author(s):  
Jianzhong Ji ◽  
Peter Chang ◽  
Mark E. Pennesi ◽  
Zhuo Yang ◽  
Jian Zhang ◽  
...  

Author(s):  
Shadi Rajabi ◽  
Craig A. Simmons ◽  
C. Ross Ethier

Glaucoma, a chronic optic neuropathy, is the second most common cause of blindness, affecting 67 million people worldwide. The damage in glaucoma occurs at the optic nerve head (ONH), where the axons of the retinal ganglion cells leave the eye posteriorly. Glaucoma is frequently associated with elevated intraocular pressure (IOP), and visual field loss can be prevented by significant lowering of IOP. Hence, the role of pressure in glaucoma is important. Unfortunately, the mechanism by which pressure leads to vision loss in glaucoma is very poorly understood.


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