Effect of Sympathetic Denervation on Rabbit Choroidal Blood Flow

Abstract

In this study we demonstrate the existence of sympathetic innervation and compare the effect of unilateral or bilateral superior cervical sympathectomy on albino rabbit choroidal blood flow (CBF) during changes in perfusion pressure (PP). Forty albino rabbits weighing between 2.0 and 3.0 kg were randomly divided into three groups. The bilateral sympathectomy group (group S) included 10 rabbits (20 eyes) that received bilateral sympathectomy 1 week prior to the study. The unilateral sympathectomy group (group U) included 20 rabbits (20 eyes) that received unilateral sympathectomy 1 week prior to the study. Only the eyes ipsilateral to sympathectomy were utilized. The other 10 rabbits (20 eyes) served as controls (group N), each received the same procedure as the experimental groups except that the superior cervical ganglion (SCG) was preserved. The blood cell flux (PF), velocity (V), and concentration of moving blood cells (CMBC) were recorded simultaneously by means of a laser Doppler flowmeter (Perimed PF4001), while the intraocular pressure was increased linearly with a syringe pump. When the PP decreased steadily, the PF, V, and CMBC remained constant until PP <55 mm Hg, then decreased proportionally to the PP. When the PP decreased from 75 to 0 mm Hg, the PF, V and CMBC decreased from 100 to 6.87 ± 0.97%, 8.44 ± 0.92%, and 18.67 ± 0.91% in group N, to 18.56 ± 1.62%, 19.30 ± 1.84%, and 38.02 ± 9.10% in group U, and to 18.38 ± 2.89%, 16.78 ± 1.48%, and 34.58 ± 4.42% in group S. The changes in PF, V, and CMBC were similar in groups S and U. Both group S and U had higher PF, V, and CMBC values than group N at comparable PPs below 55 mm Hg. These results indicate that the SCG plays a role in CBF regulation. Both unilateral and bilateral sympathectomy led to a higher PF in both groups S and U rabbits, indicating increased CBF while PP decreased gradually. This suggests that the rabbit choroid does not receive crossed innervation. The plateau response in each curve demonstrates the presence of autoregulation. This autoregulation was unchanged by either unilateral or bilateral sympathetic denervation.

Neural control of choroidal blood flow

“…It became increasingly evident from subsequent studies and is now widely accepted, however, that ChBF does compensate for perfusion pressure changes. For example, some degree of autoregulation with IOP elevation (which causes choroidal perfusion pressure reduction) has been noted in cats (Friedman, 1970; Weiter et al, 1973), rabbits (Chou et al, 2002), and humans (Riva et al, 1997a,b). When ocular perfusion pressure is experimentally reduced by lowering BP rather than by raising IOP, studies in rabbits have shown that stable ChBF over a blood pressure (BP) range of 40–50 mm Hg below basal BP is observed (Kiel and Shepherd, 1992).…”

“…Several studies have examined the impact on ChBF of removing the sympathetic input to choroid. Using LDF, Chou and coworkers found no evident increase in ChBF at basal perfusion pressures in rabbits one week after bilateral removal of the superior cervical ganglion (SCG) (Chou et al, 2000), or one week after unilateral removal of the SCG (Chou et al, 2002). Zhan et al (2002) reported that basal ChBF in rabbits was also unchanged 24 h after sympathetic denervation by SCG removal.…”

Defective Choroidal Blood Flow Baroregulation and Retinal Dysfunction and Pathology Following Sympathetic Denervation of Choroid

“…Sympathetic noradrenergic nerve fibers from SCG innervate choroid, 1 , 2 , 26 – 32 and mediate decreases in ChBF 33 – 39 via alpha-adrenergic receptors, 6 , 38 – 44 as well as by NPY action. 45 , 46 Although earlier studies in rabbits using labeled microspheres had reported that sympathetic denervation does not substantially affect basal choroidal tone at normal BP, 6 , 7 , 9 , 17 , 47 more recent studies have shown increased choroidal vessel luminal diameters 6 weeks after cranial sympathetic transection in rats, 48 and choroidal expansion by 6 weeks after superior cervical ganglion removal in mice. 49 Consistent with the vasodilatory effect of removal of sympathetic vasoconstrictory tone implied by the latter studies, we observed by LDF that basal ChBF was slightly but persistently elevated in SCGx compared to sham eyes (by 14.5%) at 2 to 3 months after surgery.…”

“… 16 SCGx efficacy was confirmed by ptosis, and immunohistochemical evaluation of sympathetic innervation of choroid. Although the SCG projection to choroid is largely unilateral, 17 bilateral SCGx ensured all sympathetic innervation was eliminated. For two rats, we cut the ascending sympathetic trunk to the SCG bilaterally, to evaluate preganglionic deafferentation of SCG.…”

Stimulation of Baroresponsive Parts of the Nucleus of the Solitary Tract Produces Nitric Oxide-mediated Choroidal Vasodilation in Rat Eye

“…Our previous work has shown that ChBF can reliably be measured transclerally, using LDF (Fitzgerald et al, 1990 , 1996 , 2001 , 2005 ; Zagvazdin et al, 1996b ; Reiner et al, 2010b ). The principles of LDF have been described in detail by others (Haumschild, 1986 ; Bonner and Nossal, 1990 ), and this approach provides an accepted relative index of ChBF, as well as relative indices of choroidal blood volume (ChBVol) and choroidal blood velocity (ChBVel), whose product is ChBF and which have been shown to linearly relate to ChBF as measured by LDF (Riva et al, 1994 ; Shepherd et al, 1997 ; Grunwald et al, 1998a ; Chou et al, 2002 ; Gugleta et al, 2002 ; Garhöfer et al, 2005 ; Tonini et al, 2010 ; Xu et al, 2010 ; Falsini et al, 2011 ). Moreover, hemodilution studies in model systems have shown that blood flow as assessed by laser Doppler scales linearly with red blood cell count (Nilsson et al, 1980 ; Fischer et al, 1985 ; Almond and Wheatley, 1992 ).…”