Abstract
Purpose :
The choroidal vasculature is innervated by sympathetic vasoconstrictory nerve fibers that prevent overperfusion of outer retina during high blood pressure (BP). We have shown that such overperfusion following sympathetic denervation of choroid causes oxidative stress and harms retina. In the present study, we assessed if sympathetic denervation of choroid leads to outer retinal and choroidal pathology that resembles that in age-related macular degeneration (AMD). For comparison, we also evaluated the impact of impairing adaptive parasympathetic vasodilatory control of choroidal blood flow (ChBF) by lesioning the preganglionic neurons in the superior salivatory nucleus (SSN) that control pterygopalatine neurons innervating choroid.
Methods :
Some rats received right superior cervical ganglionectomy (SCGx), while in others right SSN was stereotaxically lesioned. Following 4-14 month survival, rats were sacrificed, their eyes embedded in plastic, and sections examined at the light and electron microscopic levels.
Results :
By 4 months after SCGx, choroid showed thickening of artery and capillary basement membrane and choriocapillaris showed a reduction in fenestrations. By 8 months, Bruch’s membrane showed regional accumulation of debris in its outer collagenous layer, choriocapillaris showed widening of intercapillary pillars, and RPE showed widespread loss of basal infoldings, and regional RPE cell loss accompanied by subretinal vacuolation at intercapillary pillars. Subretinal space thickening and debris accumulation were also observed. RPE loss was associated with fewer photoreceptor cell bodies in subjacent outer nuclear layer. By comparison, SSN lesions yielded no evident pathologies in choroid, choriocapillaris, Bruch’s membrane or RPE, but increased luminal size of the vessels of the inner retinal vasculature was observed.
Conclusions :
Our studies show that sympathetic denervation of choroid leads to pathologies in choroid, choriocapillaris, Bruch’s membrane, RPE and photoreceptors. As a sympathetic ChBF baroregulatory defect has been observed in young individuals with AMD-causing CFH polymorphisms (Told et al., PLoS One 2013), our results suggest this regulatory defect can lead to AMD-like outer retinal pathology. The absence of outer retinal pathology after disruption of parasympathetic control of choroid may stem from a compensatory increase in inner retinal blood flow.
This is a 2020 ARVO Annual Meeting abstract.