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F. Mantelli, A. Micera, M. Sacchetti, S. Speranza, A. Lambiase, G. Petrachi, S. Bonini; Neurogenic Inflammation of the Ocular Surface. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4869.
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Neurogenic inflammation plays a crucial role in allergic and autoimmune diseases. Sensory and autonomic nerve fibers release neuromediators, which trigger and modulate neurogenic inflammation. Although the cornea is the most densely innervated tissue of the human body, little is known about the role of neuromediators at the ocular surface. We aimed at evaluating the role of the following neuromediators in inflammatory conditions of the ocular surface: Substance P (SP), Calcitonine Gene Related Peptide (CGRP), Neuropeptide Y (NPY) and Vasoactive Intestinal Peptide (VIP).
19 patients with dry eye (4M, 15F; mean age 64±14 years), 14 with allergic conjunctivitis (5F, 9M, mean age 30±9 years) in non-active phase and 12 healthy subjects (8 males and 4 females; mean age 41±21 years), were included in this study. Conjunctival provocation test (CPT) with allergen was performed in all allergic patients. Tear samples were collected and the tear content of VIP, NPY, CGRP and SP was measured by ELISA at baseline and after CPT. Mann-Whitney U-test was used to compare neuromediators’ levels and Spearman-rho correlation analysis was performed to identify relationships with clinical parameters.
No significant differences were observed between healthy and allergic patients without symptoms. In allergic patients SP, CGRP and VIP were significantly higher after CPT (SP: 3.2 (0.1-5.9) g/ml versus 5.1 (0.8-7.4)ng/ml, p=0.018; CGRP:5.5 (1.9-10.3)ng/ml versus 6 (2.4-10.9) ng/ml; p=0.006; VIP: 3.9 (2.7-5.6) g/ml versus 5.3 (2.3-7.5)ng/ml, p=0.019). Patients with dry eye showed a significant decrease in tear levels of CGRP (median: 3 ng/ml (range: 0.2-9.3 ng/ml) vs. 5.8 ng/ml (2.5-10.5 ng/ml); p=0.001) and NPY (1.6 ng/ml (0.2-9.6 ng/ml) vs 4.3 ng/ml (1.6-33.1 ng/ml); p=0.015). In dry eye patients, CGRP and NPY showed a direct correlation with Schirmer test (p=0.010, p=0.042; respectively) and an inverse correlation with Oxford score (p<0.001, p=0.006), and NPY inversely correlated to tear film break-up time (p=0.006).
Locally-released neuromediators may be crucial to modulate inflammatory responses of the ocular surface. Further studies will be needed to identify the specific role of different neuromediators in ocular surface diseases.
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