Abstract
Purpose :
Light-evoked reflectance decreases in the retina, seen using intrinsic signal optical imaging, are of outer retinal origin and dominated by hemodynamics. The specific pathways underlying this neurovascular response (and imaged signals) are unknown. Most previous studies of retinal neurovascular coupling have been in vitro and presume an inner retinal origin. We sought to dissect the role of signaling pathways in the stimulus-evoked neurovascular responses in vivo through intravitreal injections of selected agents.
Methods :
Using a modified fundus camera, the retinas of adult anesthetized cats were stimulated with visible (550nm) patterned stimuli and illuminated in the near-infrared (700-900nm), while intrinsic optical signals were recorded with a CCD camera. Intravitreal injections included TTX, APB/PDA, adenosine, NECA (P1 agonist), PPOH (EET inhibitor), indomethacin (COX inhibitor), HET0016 (20-HETE inhibitor), L-NAME (NOS inhibitor), and Verapamil (L-type calcium channel blocker).
Results :
Unlike pharmacologic injections designed to block retinal neural activity, at the ganglion cell level (TTX) or inner retina (APB/PDA), injections of drugs that disrupt neurovascular coupling have a profound effect on the light-evoked retinal imaging signals. Our data suggest that the arachidonic pathways are obligatory for the light-induced hemodynamic response in the retina since EET and prostaglandin inhibitors abolished the imaging signal, while a 20-HETE inhibitor (HET0016) decreased the signal amplitude. Inhibiting nitric oxide (NO) production using L-NAME demonstrated a lesser contribution for NO in the imaging pathways. Verapamil, an L-type calcium channel blocker, reduced the imaging signal amplitude, suggesting that the light-induced neurotransmitter release contributes to the reflectance change signal.
Conclusions :
These results indicate that arachidonic acid metabolites play a critical role in the light-evoked hyperemic response. Nitric oxide synthesis blockers yielded minimal effects. Purinergic pathways also play contribute to the imaging signal, but further investigation is required to show how specific purinergic receptors influence the signal.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.