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

• Published in: Frontiers in neurology Vol. 12
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 13-04-2021
• Subjects: Cav2.3-deficient mice; dynamic retinal vessel analysis; in vivo retinal vessel analysis; Neurology; neurovascular coupling; voltage- gated Ca2+ channels
• ISSN: 1664-2295; 1664-2295
• DOI: 10.3389/fneur.2021.659890

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 Ca
2+
-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
v
2.3-competent (Ca
v
2.3
[+/+]
) and -deficient (Ca
v
2.3
[−/−]
) 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 (AUC
art
/AUC
ven
) during flicker application, mean maximum dilation (mMD
art
/mMD
ven
) and time to maximum dilation (tMD
art
/tMD
ven
) during the flicker, dilation at flicker cessation (DFC
art
/DFC
ven
), mean maximum constriction (mMC
art
/mMC
ven
), time to maximum constriction (tMC
art
/tMC
ven
) after the flicker and reactive magnitude (RM
art
/RM
ven
).
Results:
A total of 33 retinal scans were conducted in 22 Ca
v
2.3
[+/+]
and 11 Ca
v
2.3
[−/−]
mice. Ca
v
2.3
[−/−]
mice were characterized by attenuated and partially reversed arterial and venous responses, as reflected in significantly lower AUC
art
(
p
= 0.031) and AUC
ven
(
p
= 0.047), a trend toward reduced DFC
art
(
p
= 0.100), DFC
ven
(
p
= 0.100), mMD
ven
(
p
= 0.075), and RM
art
(
p
= 0.090) and a trend toward increased tMD
art
(
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 Ca
v
2.3 channels could be involved in NVC and may contribute to the impairment of vasomotor responses under pathophysiological conditions.