Neural Control of Choroidal Blood Flow

University Of Tennessee Health Sci Ctr, Memphis TN

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Abstract

DESCRIPTION (provided by applicant): In prior studies in birds, we found that parasympathetic input to choroidal blood vessels adaptively matches choroidal blood flow (ChBF) to retinal need and is thereby critical for retinal health. Studies are proposed here to explore this premise in a mammalian species (rats), and in particular determine the role of facial parasympathetic circuitry in ChBF stability during systemic blood pressure (BP) fluctuation (baroregulation) and in light-mediated control of ChBF. In Aim 1, we will characterize the central circuitry mediating ChBF control via the facial nucleus using conventional anterograde pathway tracing methods combined with selective retrograde transneuronal labeling, using pseudorabies virus (PRV), of choroidal facial nucleus preganglionic parasympathetic neurons. Our goals will be to: 1A) confirm our prior findings with higher-order PRV labeling that the hypothalamic paraventricular nucleus (PVN) and the nucleus of the solitary tract (NTS), which are sensitive to systemic BP, project to choridal facial nucleus parasympathetic neurons; and 1B) determine if any visual brainstem areas project to choroidal facial nucleus parasympathetic neurons. We will also use pairs of conventional and transneuronal retrograde tracers to determine if choroidal and cerebral blood flow are controlled by the same facial circuit neurons. In Aim 2, we will use transcleral laser Doppler flowmetry (LDF) and brain stimulation to determine if the PVN and NTS do control ChBF via facial nucleus. The peripheral vasoactive agents mediating the ChBF increases (likely to be VIP, NO and acetylcholine) will be assessed pharmacologically. The ability of suprachiasmatic nucleus stimulation or retinal illumination to elicit facial nucleus-mediated ChBF increases will also be examined. In Aim 3, we will determine by immediate early gene induction if the facial circuit controlling ChBF is responsive to systemic BP, and use transcleral LDF and facial nucleus preganglionic neuron inactivation to characterize its role in baroregulation, in Aim 4, we will determine by central lesions of the facial preganglionic neurons and subsequent histological assessment if the facial circuit controlling ChBF is critical for maintaining retinal health. Understanding the role of neural control of ChBF in support of the retina may contribute to understanding how diseases affecting the vasculature (e.g. aging, senile macular disease, hypertension, and glaucoma) damage retina, which may provide therapeutic insights.