Enhanced Endothelin-1 Mediated Vasoconstriction of the Ophthalmic Artery May Exacerbate Retinal Damage after Transient Global Cerebral Ischemia in Rat.
Cerebral vasculature is often the target of stroke studies. However, the vasculature supplying the eye might also be affected by ischemia. The aim of the present study was to investigate if the transient global cerebral ischemia (GCI) enhances vascular effect of endothelin-1 (ET-1) and 5-hydroxytryptamine/serotonin (5-HT) on the ophthalmic artery in rats, leading to delayed retinal damage. This was preformed using myography on the ophthalmic artery, coupled with immunohistochemistry and electroretinogram (ERG) to assess the ischemic consequences on the retina. Results showed a significant increase of ET-1 mediated vasoconstriction at 48 hours post ischemia. The retina did not exhibit any morphological changes throughout the study. However, we found an increase of GFAP and vimentin expression at 72 hours and 7 days after ischemia, indicating Müller cell mediated gliosis. ERG revealed significantly decreased function at 72 hours, but recovered almost completely after 7 days. In conclusion, we propose that the increased contractile response via ET-1 receptors in the ophthalmic artery after 48 hours may elicit negative retinal consequences due to a second ischemic period. This may exacerbate retinal damage after ischemia as illustrated by the decreased retinal function and Müller cell activation. The ophthalmic artery and ET-1 mediated vasoconstriction may be a valid and novel therapeutic target after longer periods of ischemic insults.
Department of Clinical Sciences, Division of Experimental Vascular Research, Lund University, Lund, Sweden.
Frank W
FW
Blixt
Department of Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet, Glostrup, Denmark.
Sara Ellinor
SE
Johansson
Department of Ophthalmology, Glostrup Research Institute, Rigshospitalet, Glostrup, Denmark.
Leif
L
Johnson
Department of Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet, Glostrup, Denmark.
Kristian Agmund
KA
Haanes
Department of Clinical Sciences, Division of Experimental Vascular Research, Lund University, Lund, Sweden.|Department of Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet, Glostrup, Denmark.
Karin
K
Warfvinge
Department of Clinical Sciences, Division of Experimental Vascular Research, Lund University, Lund, Sweden.|Department of Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet, Glostrup, Denmark.
Lars
L
Edvinsson
D000818:Animals; D002645:Chickens; D004596:Electroretinography; D019332:Endothelin-1 / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000473:pathology*; D008297:Male; D055254:Night Vision; D009880:Ophthalmic Artery / Q000378:metabolism* / Q000502:physiology*; D017208:Rats, Wistar; D012160:Retina / Q000378:metabolism* / Q000473:pathology*; D014661:Vasoconstriction; D014746:Vimentin / Q000378:metabolism
D019332:Endothelin-1; D005904:Glial Fibrillary Acidic Protein; D014746:Vimentin