Retinal Vessel Responses to Flicker Stimulation Are Impaired in Cav2.3-Deficient Mice—An in-vivo Evaluation Using Retinal Vessel Analysis (RVA)

Abstract

Objective: Metabolic demand increases with neuronal activity and adequate energy supply is ensured by neurovascular coupling (NVC). Impairments of NVC have been reported in the context of several diseases and may correlate with disease severity and outcome. Voltage-gated Ca2+-channels (VGCCs) are involved in the regulation of vasomotor tone. In the present study, we compared arterial and venous responses to flicker stimulation in Cav2.3-competent (Cav2.3[+/+]) and -deficient (Cav2.3[−/−]) mice using retinal vessel analysis.Methods: The mice were anesthetized and the pupil of one eye was dilated by application of a mydriaticum. An adapted prototype of retinal vessel analyzer was used to perform dynamic retinal vessel analysis. Arterial and venous responses were quantified in terms of the area under the curve (AUCart/AUCven) during flicker application, mean maximum dilation (mMDart/mMDven) and time to maximum dilation (tMDart/tMDven) during the flicker, dilation at flicker cessation (DFCart/DFCven), mean maximum constriction (mMCart/mMCven), time to maximum constriction (tMCart/tMCven) after the flicker and reactive magnitude (RMart/RMven).Results: A total of 33 retinal scans were conducted in 22 Cav2.3[+/+] and 11 Cav2.3[−/−] mice. Cav2.3[−/−] mice were characterized by attenuated and partially reversed arterial and venous responses, as reflected in significantly lower AUCart (p = 0.031) and AUCven (p = 0.047), a trend toward reduced DFCart (p = 0.100), DFCven (p = 0.100), mMDven (p = 0.075), and RMart (p = 0.090) and a trend toward increased tMDart (p = 0.096).Conclusion: To our knowledge, this is the first study using a novel, non-invasive analysis technique to document impairment of retinal vessel responses in VGCC-deficient mice. We propose that Cav2.3 channels could be involved in NVC and may contribute to the impairment of vasomotor responses under pathophysiological conditions.

The Role of the Glycocalyx in the Pathophysiology of Subarachnoid Hemorrhage-Induced Delayed Cerebral Ischemia

“…The above-mentioned processes cumulatively result in dysfunction of NVC following aSAH. Preclinical and clinical studies have indeed revealed dysregulation of vasodilatation and even pathological vasoconstriction in response to different stimuli in experimental aSAH models and patients (Britz et al, 2007;Budohoski et al, 2012;Koide et al, 2013a;Balbi et al, 2017;Neumaier et al, 2021). Moreover, DCI has been associated with decreased vasoreactivity of the middle cerebral artery measured 4 to 10 days after ictus in a prospective clinical study including 34 patients with aSAH (Carrera et al, 2010).…”

Endothelial dysfunction in retinal vessels of hemodialysis patients compared to healthy controls

“…Throughout the last years DVA has been adjusted to be used in rodents. Only recently a study was able to prove an involvement of voltage-gated calcium channels in knock-out mice 21 . Further in-vivo studies in rodents are needed to clarify the role of inflammation in the pathophysiology of retinal microvascular dysfunction.…”

Methods to measure blood flow and vascular reactivity in the retina

“…Inhibition of NO synthase during isometric exercise in healthy humans reduced retinal venous diameter and responsiveness ( 51 ). Recently, the application of a prototype of an adapted RVA in laboratory animals was introduced to evaluate neurovascular coupling in the murine retina ( 52 , 53 ).…”