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Chunyan Li, Catherine Taylor, Natalie Guley, Nobel Del Mar, Malinda EC Fitzgerald, Anton Reiner; Effect of Neuronal Nitric Oxide Synthase Deletion on Choroidal Blood Flow and Retinal Morphology and Function. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3039.
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© ARVO (1962-2015); The Authors (2016-present)
Basal and adaptive vasodilatory control of choroidal blood flow (ChBF) is mediated by parasympathetic innervation from the pterygopalatine ganglion (PPG), which uses nitric oxide (NO) as a vasodilator, as well as vasoactive intestinal polypeptide (VIP). We examined the impact of hemizygous or homozygous deletion of the enzyme responsible for NO synthesis by the PPG, namely neuronal nitric oxide synthase (nNOS), on ChBF and on retinal structure and function.
The following assessments were made in male and female WT, nNOS+/-, and nNOS-/- mice from 90-500 days of age: 1) ChBF measured by transscleral Laser Doppler Flowmetry while monitoring arterial blood pressure (ABP); 2) visual acuity as measured using OptoMotry; and 3) retinal thickness as measured in plastic-embedded sections using StereoInvestigator.
Basal ChBF was ~60% of WT in both nNOS+/- and nNOS-/- mice at 3 months of age, but baroregulation (i.e. stable basal ChBF during ABP fluctuation) appeared to be intact. Visual acuity, thickness of retinal layers and photoreceptor abundance did not differ among WT, nNOS+/- and nNOS-/- mice at 3 months of age. By contrast, visual acuity was only 60% of age-matched WT in nNOS+/- mice at 200-500 days of age. Surprisingly, visual acuity in nNOS-/- mice at 200-500 days of age was only reduced to ~85% of WT. A significant age-related decline in photoreceptor abundance and retinal ganglion cell layer thickness was seen over the 200-500 day range in nNOS+/- mice, but not in nNOS-/- mice. Total retinal and RPE thickness were reduced in both nNOS+/- and nNOS-/- mice compared to WT at 200 to 500 days of age.
Our studies indicate that basal ChBF is diminished in nNOS+/- and nNOS-/- mice, but baroregulation seems intact. Age-related decline in visual acuity was observed in both nNOS+/- and nNOS-/- mice, but surprisingly it was more severe in nNOS+/- mice. Moreover, although retinal thinning was seen in both nNOS+/- and nNOS-/- mice, acceleration of age-related ganglion cell and photoreceptor loss beyond one year of age was only seen in nNOS+/- mice. The basis of the greater age-related decline in nNOS+/- than nNOS-/- mice is uncertain, but may stem from diminished NO-mediated free radical injury in the nNOS-/- mice. In any case, our studies suggest the important role of NO-mediated parasympathetic regulation of ChBF in the long-term maintenance of retinal health.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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