Role of Renin-Angiotensin System in Optic Neuritis

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The optic neuritis is strongly related to multiple sclerosis. During the inflammatory stages, optic neuritis may lead to serious health consequences such as visual disorder which is clinically known as neuromyelitis optica.

In a recent paper published in American Journal of Pathology, researchers at Tokyo Metropolitan Institute of Medical Science in Japan discovered a new pathway that can be targeted to restore visual impairment. They looked carefully at Renin-Angiotensin System and its role on neurodegeneration. They also studied the therapeutic potential of candesartan, an Ang II receptor antagonist, against optic neuritis.

The clinical significance of Renin-Angiotensin System is undeniable. Renin is secreted by the juxtaglomerular cells in the kidney and responsible for controlling perfusion pressure. This enzymatic system is known for carrying vital functions in a human body and disruption of its hemostasis can cause cardiovascular and renal diseases.

In the current study, Guo et al. found that Renin-Angiotensin System is responsible for regulation of neurodegeneration. They discovered that Renin-Angiotensin System carries a vital role in the progression of EAE, an animal model of multiple sclerosis. Earlier studies reported involvement of Renin-Angiotensin System in the oxidative stress-induced RGC death and the current research experimentally confirmed its association with the pathogenesis of EAE.

The research team looked at the pharmacological activity of candesartan on a MOG-induced EAE mouse model and observed that impaired visual function of the EAE mice was partially improved when treated with candesartan. According to their research findings, candesartan treatment considerably reduces the severity of EAE and delayed disease onset while with no impacts on the incidence of EAE.

Guo et al. also reported that Ang II concentrations in serum were considerably higher at the first stage of EAE mice in comparison with healthy mice, suggesting a detrimental role of Ang II during EAE. Ang II also upregulated TLR4 in microglia and increased the generation of reactive oxygen species inside the paraventricular nucleus. The authors concluded that Renin-Angiotensin System is a therapeutic target for optic neuritis and other neurodegnerative diseases.

It will be interesing in the future to perform epidomiological studies to look at whether patients administered with ACE inhibitors or Ang II receptor antagonists have lower incidence of multiple sclerosis and thus protection from inflammation.


Role of Renin-Angiotensin System in Optic Neuritis

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Xiaoli Guo is a senior researcher at Visual Research Project in Tokyo Metropolitan Institute of Medical Science in Japan. She graduated from Fudan University with a Master degree in Biophysics and Physiology in 1997 in Shanghai, China. Afterward, she attended Tokyo University of Agriculture and Technology and earned her Ph.D. in United Graduate School of Agricultural science in 2002. She then moved to the United States and conducted a postdoctoral fellowship in the laboratory of Dr. John Troy at the Biomedical Engineering Department in Northwestern University in Evanston, Chicago.

Dr. Guo joined Visual Research Project, headed by Dr. Takayuki Harada, in 2006. Since then she has been working on elucidating the mechanism and potential treatment strategies for multiple sclerosis and optic neuritis by using genetically modified mice and existing drugs and chemicals. Her work also includes promoting neuroprotection and neuroregeneration for neurodegenerative diseases such as normal tension glaucoma.

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Guo, X., Namekata, K., Kimura, A., Harada, C., & Harada, T. (2017). The Renin-Angiotensin System Regulates Neurodegeneration in a Mouse Model of Optic Neuritis. The American journal of pathology, 2017, 187(12), 2876-2885.