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Jeremias Gaston Galletti, Mauricio Guzman, Irene Keitelman, Florencia Sabbione, Analía S Trevani, Mirta N Giordano; Corneal burn in one eye leads to neurogenic conjunctival inflammation of the fellow eye. Invest. Ophthalmol. Vis. Sci. 2016;57(12):320.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the effect that a corneal injury in one eye has on the conjunctival immune response of the fellow eye and a potential neural mechanism involved, as both ocular surfaces are usually considered immunologically independent but recent findings suggest otherwise.
A controlled corneal burn with NaOH was induced in the left eye of Balb/c mice (day 1), and the conjunctival immune response of the right eye was assessed by either instilling ovalbumin (OVA) daily on days 2-5 or by a subconjunctival injection of allogeneic B16 tumor cells in the right eye on day 1. OVA-specific T cell responses were measured by delayed-type-hypersensitivity (DTH) assays (day 15) after s.c. immunization with OVA in adjuvant (day 8), and tumor development was recorded for up to 3 weeks. For some experiments, aprepitant (substance P antagonist) was instilled daily on the right eye on days 1-7, and for others, the corneal burn was replaced by instillation of capsaicin (agonist of TRPV1 receptors in afferent nerve fibers) on days 1-3.
Uninjured mice that received OVA in the right eye developed blunted DTH responses (50±9%, p<0.05) and their T cells suppressed a DTH response after local adoptive transfer (58±4%, p<0.05), whereas mice with a corneal burn in the left eye failed to do so (DTH 86±11%, ns; adoptive transfer 122±9%, ns). Consistently, rejection of a subconjunctival tumor was markedly increased by a contralateral corneal burn (56% vs 89%, p<0.05). Disruption of contralateral conjunctival tolerance to OVA or increased contralateral tumor rejection induced by a left corneal burn was reversed by aprepitant instilled on the right eye (p<0.05). Conversely, capsaicin instillation on the left eye elicited in the right eye effects similar to those observed for the alkali-induced corneal burn.
An alkali-induced corneal burn destroys the superficial cornea, which includes abundant nerve fibers. This lesion is sufficient to drastically alter the immune response of the fellow conjunctiva, as shown by the increased antigen-specific responses to OVA and the enhanced tumor rejection. A neurogenic inflammatory reflex seems to be involved, as the effect on the contralateral ocular surface can be induced by ipsilateral instillation of capsaicin and blocked by contralateral instillation of a substance P antagonist. These findings highlight the immunological interdependence of the ocular surfaces.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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