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Daniel Y Tso, Momotaz Begum; Noninvasive functional retinal imaging disrupted by pharmacologic manipulation of neurovascular coupling pathways.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4123.
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Intrinsic signal optical imaging studies have shown the existence of stimulus-evoked signals in the retina that are likely to be of outer retinal origin. Additional studies have also shown that such reflectance change signals are dominated by hemodynamics. The linkage between this stimulus-driven retinal activity and the resulting hemodynamic basis of the measured reflectance changes is a form of neurovascular coupling. However the precise chain of mechanisms in the retina whereby photoreceptor activation leads to a vascular response is unknown. Most previous studies of neurovascular coupling in the retina have been in vitro. In the present study, we sought to dissect the role of several prospective signaling pathways in the observed stimulus-evoked neurovascular responses in vivo through intravitreal injections of selected agonists, antagonists and blockers, while imaging these retinal intrinsic signals.
Animals and Preparation. Adult cats were anesthetized, paralyzed and positioned in a stereotaxic. Using a modified fundus camera, the retina was stimulated with visible (550nm) patterned stimuli and illuminated in the near-infrared (700-900nm), while intrinsic optical signals were recorded with a CCD camera.<br /> <br /> Drug-injections. Intravitreal injections included suramin (purinergic antagonist), HET0016 (20-HETE inhibitor), PPOH (EET inhibitor) and NECA (adenosine agonist).
Previous retinal imaging studies using intravitreal injections of blockers of inner retinal function (e.g. TTX, PDA, APB) yielded little impact on the retinal imaging signals. However in the present study, each drug selected to interfere with a particular neurovascular coupling pathway had profound impact on the observed retinal imaging signals. In some cases, the sign of the observed retinal imaging signal changed from negative to positive.
This novel functional retinal imaging technique is shown to reveal outer retinal function through its impact on hemodynamics via the neurovascular coupling pathways. These studies help establish the chain of retinal events from light absorption to observed changes in retinal reflectance in vivo. It is anticipated that an understanding of the underlying neural, biophysical and signaling mechanisms will help determine the utility of this method for studies of retinal function, health and related clinical applications.
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