AUTHOR=Neumaier Felix , Kotliar Konstantin , Haeren Roel Hubert Louis , Temel Yasin , Lüke Jan Niklas , Seyam Osama , Lindauer Ute , Clusmann Hans , Hescheler Jürgen , Schubert Gerrit Alexander , Schneider Toni , Albanna Walid 

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

JOURNAL=Frontiers in Neurology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.659890

DOI=10.3389/fneur.2021.659890

ISSN=1664-2295

ABSTRACT=<p><bold>Objective:</bold> 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 Ca<sup>2+</sup>-channels (VGCCs) are involved in the regulation of vasomotor tone. In the present study, we compared arterial and venous responses to flicker stimulation in Ca<sub>v</sub>2.3-competent (Ca<sub>v</sub>2.3<sub>[+/+]</sub>) and -deficient (Ca<sub>v</sub>2.3<sub>[−/−]</sub>) mice using retinal vessel analysis.</p><p><bold>Methods:</bold> 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 (AUC<sub>art</sub>/AUC<sub>ven</sub>) during flicker application, mean maximum dilation (mMD<sub>art</sub>/mMD<sub>ven</sub>) and time to maximum dilation (tMD<sub>art</sub>/tMD<sub>ven</sub>) during the flicker, dilation at flicker cessation (DFC<sub>art</sub>/DFC<sub>ven</sub>), mean maximum constriction (mMC<sub>art</sub>/mMC<sub>ven</sub>), time to maximum constriction (tMC<sub>art</sub>/tMC<sub>ven</sub>) after the flicker and reactive magnitude (RM<sub>art</sub>/RM<sub>ven</sub>).</p><p><bold>Results:</bold> A total of 33 retinal scans were conducted in 22 Ca<sub>v</sub>2.3<sub>[+/+]</sub> and 11 Ca<sub>v</sub>2.3<sub>[−/−]</sub> mice. Ca<sub>v</sub>2.3<sub>[−/−]</sub> mice were characterized by attenuated and partially reversed arterial and venous responses, as reflected in significantly lower AUC<sub>art</sub> (<italic>p</italic> = 0.031) and AUC<sub>ven</sub> (<italic>p</italic> = 0.047), a trend toward reduced DFC<sub>art</sub> (<italic>p</italic> = 0.100), DFC<sub>ven</sub> (<italic>p</italic> = 0.100), mMD<sub>ven</sub> (<italic>p</italic> = 0.075), and RM<sub>art</sub> (<italic>p</italic> = 0.090) and a trend toward increased tMD<sub>art</sub> (<italic>p</italic> = 0.096).</p><p><bold>Conclusion:</bold> 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 Ca<sub>v</sub>2.3 channels could be involved in NVC and may contribute to the impairment of vasomotor responses under pathophysiological conditions.</p>