Retinal Vessel Responses to Flicker Stimulation Are Impaired in Ca 2.3-Deficient Mice-An in-vivo Evaluation Using...

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 Ca_v2.3-competent (Ca_v2.3_[+/+]) and -deficient (Ca_v2.3_[-/-]) 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_v2.3_[+/+] and 11 Ca_v2.3_[-/-] mice. Ca_v2.3_[-/-] 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_v2.3 channels could be involved in NVC and may contribute to the impairment of vasomotor responses under pathophysiological conditions.