- 著者
- Ryo Kondo Ayuki Nakano Daiki Asano Akane Morita Shiho Arima Asami Mori Kenji Sakamoto Tohru Nagamitsu Tsutomu Nakahara
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Biological and Pharmaceutical Bulletin (ISSN:09186158)
- 巻号頁・発行日
- vol.43, no.5, pp.859-863, 2020-05-01 (Released:2020-05-01)
- 参考文献数
- 26
Pathological angiogenesis is a leading cause of blindness in several retinal diseases. The key driving factor inducing pathological angiogenesis is the pronounced hypoxia leading to a marked, increased production of vascular endothelial growth factor (VEGF). The aim of this study was to determine whether the abnormal vascular growth occurs in a manner dependent on the degree of the vascular defects. Vascular defects of two different degrees were created in the retina by subcutaneously treating neonatal rats with the VEGF receptor (VEGFR) tyrosine kinase inhibitor KRN633 on postnatal day (P) 4 and P5 (P4/5) or P7 and P8 (P7/8). The structure of the retinal vasculature changes was examined immunohistochemically. Prevention of vascular growth and regression of some preformed capillaries were observed on the next day, after completion of each treatment (i.e., P6 and P9). The vascular regrowth occurred as a result of eliminating the inhibitory effect on the VEGFR signaling pathway. KRN633 (P4/5)-treated rats exhibited a retinal vasculature with aggressive intravitreal neovascularization on P21. On the other hand, the appearance of tortuous arteries is a representative vascular pathological feature in retinas of KRN633 (P7/8)-treated groups. These results suggest that an interruption of the retinal vascular development at different time points induces different vascular pathological features in the retina. Pharmacological agents targeting the VEGF signaling pathway are useful for creating an abnormal retinal vasculature with various pathological features in order to evaluate the efficacy of anti-angiogenic compounds.
- 著者
- Tsutomu Nakahara Asami Mori Yuki Kurauchi Kenji Sakamoto Kunio Ishii
- 出版者
- (公社)日本薬理学会
- 雑誌
- Journal of Pharmacological Sciences (ISSN:13478613)
- 巻号頁・発行日
- pp.13R03CP, (Released:2013-09-25)
- 参考文献数
- 57
- 被引用文献数
- 10 38
Increasing evidence suggests that the complex interactions among multiple cell types including neuronal, glial, and vascular cells, are critical for maintaining adequate cerebral blood flow that is necessary for normal brain function and survival. The disturbance of these interactions contributes to the pathogenesis of central nervous system disorders such as stroke and Alzheimer’s disease. The retina is part of the central nervous system, and the properties of vasculature in the retina are similar to those in the brain. The interactions among multiple cell types in the retina also play an important role in the maintenance of tissue homeostasis, and the impairment of interactions can contribute to the onset and/or progression of retinal diseases. In this review, we describe the neurovascular interactions in the retina and alternations of interactions in pathological conditions such as diabetic retinopathy and glaucoma.