Purchase this article with an account.
Chunyan Li, Malinda EC Fitzgerald, Nobel Del Mar, Corey Haughey, Anton Reiner; Retinal and choroidal abnormalities following sympathetic denervation of choroid. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4198.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The choroidal vasculature is heavily innervated by sympathetic vasoconstrictory and parasympathetic vasodilatory nerve fibers. As the major blood supply to outer retina, the choroid is crucial for retinal function and health. We determined if sympathetic denervation of choroid impairs choroidal blood flow (ChBF) regulation, and harms retina.
Rats received bilateral superior cervical ganglionectomy (SCGx), which depletes the choroid of sympathetic innervation (vMat2+ and NPY+ fibers) but not parasympathetic innervation (VIP+ and NOS+ fibers), as confirmed here. The flash-evoked scotopic electroretinograph (ERG) was measured 2 months after SCGx. ChBF was assessed by Laser Doppler Flowmetry. To determine the effectiveness of ChBF baroregulation, blood pressure (BP) was raised by intraveneous L-NAME (10mg/kg). BP was measured via the femoral artery. Subsequently, eyes were harvested for histological evaluation.
The ERG b-wave amplitude was significantly reduced 2 months after SCGx, compared to sham rats. Although basal ChBF was not significantly different between SCGx rats and sham, choroidal baroregulation failed during the BP rise caused by L-NAME in SCGx rats. ChBF increases in SCGx rats were in parallel with the BP increase, while in sham rats ChBF remained stable and uncorrelated with the BP change. In the retina, Müller cell GFAP was upregulated 2.4 fold, and Iba1+ microglia were increased 3 fold in SCGx rats. Dopaminergic amacrine cell fibers in the inner plexiform layer, as detected by TH or vMat2 immmunolabeling, were significantly reduced in abundance in SCGx rats, although dopaminergic amacrine cell bodies were not. VIP+ amacrine cells were also significantly reduced in abundance in SCGx rats.
These studies indicate that sympathetic denervation of choroid impairs the ChBF baroregulatory response to increased BP, leading to choroidal overperfusion. This defect in ChBF regulation is associated with a reduction in the ERG b-wave peak, in glial activation, and in amacrine cell defects. The means by which choroidal overperfusion injures retina is uncertain. As sympathetic ChBF baroregulatory defects have been observed in young individuals with AMD-causing CFH polymorphisms (Told et al., PLoS One, 2013), our results suggest these defects may harm retina, perhaps contributing to AMD pathogenesis.
This PDF is available to Subscribers Only