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Jose L. Vega, Bruce Turpie, Sharmila Masli; Sympathetic Stimulation Contributes To Ocular Immune Privilege By Allowing Sustained Expression Of Transforming Growth Factor Beta In The Eye. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4366.
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TGF-beta is the principal molecule mediating immune privilege in the eye. Previously we demonstrated that ocular sympathetic denervation leads to a breakdown of ocular immune privilege associated with an acute decrease in TGF-beta content in the aqueous humor. In this study we investigated the chronicity of this effect, and directly tested the hypothesis that adrenergic stimulation of tissues and cells known to participate in ocular immune privilege, induces TGF-beta expression.
Unilateral surgical postganglionic denervation of the superior cervical ganglion (SCGX), which provides sympathetic fibers to the eye, was performed in eight-week-old male C57BL6 mice. Thirty days later, TGF-beta in the aqueous humor of dennervated eyes was quantified and compared with that of control, unmanipulated eyes. We also compared the expression of TGF-beta-1, and TGF-beta-2 in iris/ciliary body (ICB) and retinal explants immediately after sacrifice, and following 24h in culture with either 10-3M phenylephrine (PHE), an alpha-adrenergic receptor agonist, or vehicle (VE). Similar experiments were also carried out using primary retinal pigment epithelial (RPE) cell cultures.
Total TGF-beta was significantly decreased in the aqueous humor of SCGX eyes by comparison with control eyes. Furthermore, after 24h in culture, which by definition lacks sympathetic nerves, ICB and retinal explants demonstrated a precipitous decrease in TGF-beta2 expression, which could be partially prevented by adding PHE to the culture medium. TGF-beta1 expression was not significantly altered in these experiments. Importantly, PHE-treated RPE cell cultures also demonstrated a significant increase in both TGF-beta2 and TGF-beta1 expression, by comparison with VE-treated cell cultures.
Stimulation of adrenergic receptors on immune privileged tissues and cells leads to an upregulation of TGF-beta expression. Thus, sympathetic nerves may play a key role in maintaining ocular immune privilege through the up-regulation of TGF-beta.
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