Surgical Denervation of Ocular Sympathetic Afferents Decreases Local Transforming Growth Factor-β and Abolishes Immune Privilege

Mounting evidence points to a role for the sympathetic nervous system in suppressing inflammation. This role might be of specific relevance for immune privilege in the eye, where, sporadically, patients with denervated sympathetic fibers develop chronic inflammation.

Our results show that in the absence of functional sympathetic fibers, the eye loses its ability to prevent either the immune rejection of intraocular allogeneic tumor cells or the suppression of delayed type hypersensitivity responses against soluble antigens injected in the anterior chamber. This loss of immune privilege is accompanied by a decrease in the concentration of transforming growth factor-β in the aqueous humor. These results suggest that immune privilege is lost in the absence of a functional sympathetic innervation of the eye, allowing intraocular immune responses to become exaggerated. We conclude that ocular sympathetic nerves are critical for the generation and maintenance of immune privilege in the eye through the facilitation of local transforming growth factor-β production.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731140/

Cervical sympathectomy causes photoreceptor-specific cell death in the rat retina

Changes in the regulation of the vasculature of the eye may be related to some age-related ocular diseases. We have previously shown that loss of sympathetic innervation, as can normally occur with age, resulted in substantial vascular growth of the choroid. The current study was designed to determine whether changes induced by sympathetic denervation causes significant loss of photoreceptors and increased glial cell reactivity in the retina. Sympathetic denervation was performed followed by immunohistochemistry, TUNEL staining, and protein expression analysis to investigate photoreceptor loss. There was a significant reduction (30%) in photoreceptor numbers in the sympathectomized eye. This loss was due to apoptosis, as there was over a doubling in apoptotic cell numbers after sympathectomy. This loss of photoreceptors in the sympathectomized eye resulted in a significantly reduced width of the outer nuclear layer of the retina when compared to the contralateral eye. Increased glial fibrillary acidic protein (GFAP) staining was also noted after sympathectomy in the ganglion cell layer with streaking toward the bipolar cell layer. These results suggest that loss of sympathetic innervation may cause significant changes to the physiology of the choroid.

Autonomic Neuroscience
Volume 120, Issues 1-2, 15 June 2005, Pages 46-51 

morphological changes in the retina noted after sympathectomy

Results: Mice treated with PDGF inhibitor AG 1296 showed an inhibition of corneal neovascularization and a reduction of pericytes in the new formed vessels compared to untreated animals. 

Retina from sympathectomized eyes receiving saline treatment had significantly  reduced PEDF mRNA and protein expression relative to the contralateral eye receiving saline treatment. These results are similar to previous work and indicate that injection alone did not alter the results. Intravitreal PEDF administration to sympathectomized eyes returned both mRNA and protein levels to those of the contralateral eye. PEDF administration also normalized retinal morphometry to prevent the sympathectomy-induced increases 

in capillary density of the outer plexiform layers, as well as the ganglion cell layer. 

Conclusions: These results suggest that one injection of PEDF can restore protein and mRNA 

levels to those noted in an untreated animal. Furthermore, these results also indicate that 

one injection of PEDF can reverse the morphological changes noted after sympathectomy 

in the retina. 

CR:  J.J. Steinle,  B.L. Lashbrook,

files.abstractsonline.com/SUPT/25/1421/SessionPDF/119.pdf

acute mesenteric ischemia and massive intestinal infarction secondary to bilateral lumbar sympathectomy

A case of acute mesenteric ischemia and massive intestinal infarction secondary to bilateral lumbarsympathectomy and without any other apparent precipitating factors is presented. Its characteristics and findings significantly agree with those described as part of the mesenteric arterial steal syndrome. Although this syndrome was originally described as secondary to surgical revascularization of the lower extremities, experimental studies have shown that lumbar sympathectomy, by means of reducing the peripheral vascular resistance in the lower extremities, similarly causes intense hemodynamic alteration of the mesenteric circulation due to the sudeen redistribution of blood flow to the lower limbs at the expense of the mesenteric flow. When marginally compensated occlusive mesenteric arterial disease exists prior to surgery, the sudden fall in the arterial pressure gradients in this vessel can precipitate the occlusion of these arteries, resulting in mesenteric ischemia and intestinal infarction. It has also been suggested that an intense vasospamodic neurogenic reflex in the mesenteric arteries is an important factor in the pathogenesis of this syndrome.
http://www.curehunter.com/public/pubmed536170.do

sympathectomy led to an exacerbation of colitis

Substance P (SP) is a pro-inflammatory neuropeptide in colitis, whereas sympathetic neurotransmitters are anti-inflammatory at high concentrations.

Results: In all layers, Crohn’s disease patients demonstrated a loss of sympathetic nerve fibres. Sprouting of SP⁺ nerve fibres was particularly observed in the mucosa and muscular layer in Crohn’s disease. SEMA3C was detected in epithelial cells, and there was a marked increase of SEMA3C-positive crypts in the mucosa of Crohn’s disease patients compared to controls. In Crohn’s disease, the number of SEMA3C-positive crypts was negatively related to the density of mucosal sympathetic nerve fibres. Sympathectomy reduced acute DSS colitis but increased chronic DSS colitis. Sympathectomy also increased chronic colitis in Il10^−/−mice.

Gut 2008;57:911-921 doi:10.1136/gut.2007.125401

Secondary Effects of Sympathectomy - Disturbance of Sexual Function

If a portion of the autonomic nervous system is removed to modify a specific disease process, unrelated physiologic mechanisms will also be affected. The degree to which these other mechanisms may be affected often governs the selection of operative procedures. The results produced by interfering with mechanisms other than those for which the operation is performed might be designated as side-effects or secondary effects. . . .

N Engl J Med 1951; 245:121-130July 26, 1951

http://www.nejm.org/doi/full/10.1056/NEJM195107262450401