Glial Endothelin-1 Regulates Retinal Blood Flow During Hyperoxia in Cats

Youngseok Song, Taiji Nagaoka, Takafumi Yoshioka, Shinji Ono, Takanari Wada, Seigo Nakabayashi, Tomofumi Tani, Akitoshi Yoshida
2016 Investigative Ophthalmology and Visual Science  
PURPOSE. To investigate the role of endothelin-1 (ET-1) in retinal glial cells in regulating retinal blood flow (RBF) during hyperoxia in cats. METHODS. We measured the vessel diameter (D), blood velocity (V), and blood flow (F) simultaneously in first-order retinal arterioles using a laser Doppler velocimetry system. The animals were under general anesthesia during hyperoxia (100% oxygen) for 10 minutes 24 hours after intravitreal injection of L-2-aminoadipic acid (LAA), a gliotoxic compound,
more » ... r diluted hydrochloric acid (0.01 N) used as the vehicle control. We also measured the changes in the RBF after intravitreal injection of BQ-123, a specific ET type A receptor antagonist, in LAA-treated eyes. To examine if endothelin-converting enzyme-1 (ECE-1), as an ET-1generating enzyme located in retinal glial cells, immunohistochemical examinations with costaining of antiglial fibrillary acidic protein (GFAP) antibody and anti-ECE-1 antibody were performed in whole-mount retinas. RESULTS. During hyperoxia, the decreases in D, V, and F in response to hyperoxia were attenuated significantly (P < 0.01 for all comparisons) in the LAA-treated eyes compared with the vehicle control (LAA, D, À8.5 6 1.5%; V, À13.8 6 1.5%; F, À27.8 6 3.0% versus vehicle control, D, À16.8 6 1.3%; V, À26.3 6 2.0%; F, À48.9 6 2.4%). In LAA-treated eyes, intravitreal injections of BQ-123 did not change the rate of hyperoxia-induced RBF compared to LAA-treated eyes. The anti-ECE-1 antibody was costained with anti-GFAP antibody in the whole-mount retinas. CONCLUSIONS. The current findings suggest that retinal glial ET-1 may play an important role in regulating RBF during hyperoxia in cats.
doi:10.1167/iovs.16-19599 pmid:27654423 fatcat:stxgmk6w6jdstbkf2ieto2635u