Purchase this article with an account.
Kenyatta Lucas, Joan Stein-Streilein; Retinal Laser Burn induces Substance P dependent loss of Immune Privilege. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2918.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Immune inflammation in the eye is tightly regulated by multiple processes that contribute to ocular immune privilege. Many studies have shown that it is very difficult to abrogate immune privileged mechanisms including anterior chamber immune deviation (ACAID). Previously we showed that Retinal Laser Burn (RLB) abrogated ACAID, bilaterally. The purpose of our studies is to understand how RLB to one eye induces the loss of immune privilege in the non-burned eye. Here we tested the role of a neuroinflammatory peptide(substance P) in the RLB induced abrogation of ACAID.
RLB was caused by delivering four (200nm) laser spots to the right eye of mice. ACAID was induced in wild type (C57BL/6) or Substance P KO mice (B6.Cg-Tac1tm1Bbm/J). To block the activity of Substance P, the antagonist for Substance P receptor [Neurokinin 1 receptor (NK1-R)], Spantide I, was injected into the anterior chamber simultaneously with ovalbumin at various times post RLB treatment. The expression of NK1-R in the retina was assessed by histological examination of immunostained frozen tissue slides. Eyes were removed from mice that received RLB treatment, 6h, 24h and 72h earlier. Cryosections of the eyes were stained with Anti-NK1-R (Millipore Billerica, MA), and DAPI (Vector Lab, Burlingame, CA). Images were taken using a Leica TCS-SP5 confocal microscope (Leica Microsystems, Bannockburn, IL).
WT mice lost ACAID bilaterally post RLB but Substance P KO mice. Spantide I treated WT mice retained their ability to develop ACAID when given early (24h) post RLB treatment. Histologically we observed an increase of NK1-R in the retina of both eyes of mice at 6h, 24h, and 72h post RLB.
While RLB induced the loss of immune privilege (ACAID) in both eyes, blocking Substance P signaling prevented RLB induced loss of ACAID. In addition the central role of Substance P signaling in disregulating immune regulation in the eye was supported by an increase in the NK1-R early( 6 h) post RLB. Substance P is a neuronal signal that contributes to the loss of ACAID in the contralateral eye thus explaining a pathway that may cause the loss of immune regulation in the absence of a break in the blood ocular barrier or recruitment of inflammatory cells. The possibility is raised that inhibitors of Substance P may provide therapeutic maintenance of immune regulation in patients with posttraumatic injuries to the CNS or eye.
This PDF is available to Subscribers Only