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Jerry Y Niederkorn, Juan Mo, Sudha neelam, jessamee Mellon, amber Wilkerson; Corneal nerve ablation in one eye induces Langerhans cell infiltration into both eyes and abolishes immune privilege in both eyes. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5731.
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© ARVO (1962-2015); The Authors (2016-present)
Circular corneal incisions made prior to penetrating keratoplasty abrogate immune privilege for future corneal transplants, even in the opposite eye. We examined the effect of corneal incisions on the distribution and activation of corneal antigen presenting Langerhans cells (LC) and on the immune privilege of corneal allografts and immune privilege in the anterior chamber (AC).
Corneal incisions (2.0 mm) were made in the central corneal epithelium of BALB/c mice prior to receiving C57BL/6 corneal allografts or injection of antigens into AC . Immune privilege in the AC was evaluated by assessing anterior chamber-associated immune deviation (ACAID). MHC class II+, CD207+, CD11c+ LC were identified by immunofluorescence. LC were depleted by subconjunctival injection of clodronate-containing liposomes.
Corneal incisions in one eye induced activation and centripetal migration of LC into both eyes, which persisted for over 140 days. The presence of infiltrating LC abolished immune privilege in the AC as ACAID could not be induced in eyes of mice subjected to corneal incisions. ACAID was restored by purging infiltrating LC by subconjunctival injection of clodronate liposomes or by i.p. injection of the SP receptor antagonist, Spantide II. Although purging LC restored ACAID, it did not restore immune privilege of corneal grafts in mice treated with corneal incisions prior to keratoplasty. Although the neuropeptide substance P (SP) is associated with the abrogation of ACAID and the loss of immune privilege of corneal allografts, blocking SP with Spantide II did not affect LC migration in response to circular incisions.
Although placing circular incisions into the cornea in one eye abolishes both ACAID and immune privilege of corneal allografts in both eyes, the underlying mechanisms are different. SP contributes to the loss of immune privilege in the AC and for corneal allografts. However, activation and immigration of LC into the central corneal epithelium is independent of SP.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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