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Glial Endothelin-1 Regulates Retinal Blood Flow During Hyperoxia in Cats
Youngseok Song1, Taiji Nagaoka1, Takafumi Yoshioka1
1Department of Ophthalmology Asahikawa Medical University, Asahikawa, Japan.
Insights
Retinal glial cells regulate blood flow during hyperoxia via endothelin-1 (ET-1). Damaging these glial cells reduced the impact of hyperoxia on retinal blood flow (RBF) in cats.
Area of Science:
- Ophthalmology
- Physiology
- Cell Biology
Background:
- Retinal blood flow (RBF) regulation is crucial for ocular health.
- Hyperoxia can significantly alter RBF.
- The role of retinal glial cells in mediating these changes is not fully understood.
Purpose of the Study:
- To investigate the role of endothelin-1 (ET-1) in retinal glial cells in regulating RBF during hyperoxia in cats.
- To determine if ET-1 generated by glial cells contributes to hyperoxia-induced changes in RBF.
Main Methods:
- Retinal blood flow parameters (diameter, velocity, flow) were measured using laser Doppler velocimetry in cats.
- Retinal glial cells were selectively damaged using L-2-aminoadipic acid (LAA).
- Immunohistochemistry was used to identify ET-1 generating enzyme (ECE-1) in glial cells (GFAP positive).
Main Results:
- Hyperoxia caused significant decreases in RBF, which were attenuated in LAA-treated eyes.
- BQ-123, an ET-A receptor antagonist, did not alter RBF in LAA-treated eyes.
- ECE-1 was localized in glial fibrillary acidic protein (GFAP)-positive retinal glial cells.
Conclusions:
- Retinal glial cells, through ET-1, play a significant role in modulating RBF during hyperoxia in cats.
- Targeting glial ET-1 may offer a therapeutic strategy for managing hyperoxia-induced retinal vascular changes.
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, or 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-1-generating 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, -8.5 ± 1.5%; V, -13.8 ± 1.5%; F, -27.8 ± 3.0% versus vehicle control, D, -16.8 ± 1.3%; V, -26.3 ± 2.0%; F, -48.9 ± 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.
