Alterations of Tear Neuromediators in Dry Eye Disease

Abstract

To evaluate tear levels of neuromediators in patients with dry eye disease and to identify statistical correlations with the clinical findings.Methods: Nineteen patients with dry eye disease (Sjö gren syndrome, n=5 patients; non-Sjö gren syndrome, n=10; and ocular cicatricial pemphigoid, n = 4) and 12 healthy volunteers were enrolled. The eyes of all participants were evaluated by slitlamp examination, Schirmer testing, fluorescein staining, and tear film break-up time. Grading of dry eye severity was recorded. Tear samples were collected, and substance P, calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), vasoactive intestinal peptide, and nerve growth factor (NGF) concentrations were evaluated by enzyme-linked immunoassay and correlated with the clinical findings.Results: Nerve growth factor tear levels were significantly increased in participants with dry eye disease; CGRP and NPY concentrations were significantly decreased when compared with those in healthy participants. Dry eye severity showed a direct correlation with NGF and an inverse correlation with CGRP and NPY tear levels. Nerve growth factor tear levels showed a direct correlation with conjunctival hyperemia and fluorescein staining results, CGRP directly correlated with Schirmer test values, and NPY inversely correlated with tear film break-up time. Subgroup analysis showed that CGRP and NPY but not NGF were changed in autoimmune (ie, Sjö gren syndrome and ocular cicatricial pemphigoid) dry eye disease. Conclusions:The decreased tear levels of NPY and CGRP in dry eye disease are related to impaired lacrimal function, and tear levels of NGF are more closely related to corneal epithelial damage. Our findings suggest that NPY, CGRP, and NGF could become useful markers of dry eye severity.

Dry eye modifies the thermal and menthol responses in rat corneal primary afferent cool cells

“…Instead, other mediators, such as neuronal growth factors, may be involved in sensitizing corneal cool cells in the dry eye condition. Nerve growth factor (NGF) levels are increased in dry eye disease, and NGF increased cold sensitivity and the percentage of menthol-sensitive DRG neurons in culture (Babes et al 2004;Lambiase et al 2011).…”

Association between Mediators in the Tear Fluid and the Severity of Keratoconus

“…NGF is known to promote corneal nerve trophism and wound healing, and its role after refractive procedures, neurodegenerative corneal ulcers and dry eye has already been investigated [18,24,25]. The impairment of corneal innervation has been suggested to play a role in the pathogenesis of KC, and a significant reduction in NGF expression has been detected in KC corneas as part of an imbalance in the NGF signaling pathway [8,26].…”

Neuropathic ocular pain: an important yet underevaluated feature of dry eye

“…54 Furthermore, corneal epithelial damage may upregulate nerve growth factor (NGF) and decrease calcitonin generelated peptide (CGRP) levels. [55][56][57] Finally, MMP-9 levels have been shown to increase in the tears of dry eye patients. 58,59 In addition to pro-inflammatory mediators, there are anti-inflammatory mediators, such as those derived from omega 3 and 6 fatty acids (ie, resolvins and 60 ), and the presence of both pro-and antiinflammatory mediators are likely important in regulating the signs and symptoms in dry eye.…”