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    Substance P: Dry eye and allergy’s mixed signal or missing link?


    Mixed or missing?

    Substance P is an 11-amino acid peptide generally associated with neurogenic pain ranging from intense to chronic present in physiologically relevant tear concentrations.5

    Lai et al illustrated that this particular compound emanates from eosinophils, monocytes, lymphocytes, macrophages, and dendritic cells with an inflammatory trigger.6

    Subsequently, the induction of pain facilitates vasodilation that can increase vascular permeability of the surrounding tissue which stimulates mast cells and B to T lymphocytes as well as acts as a chemotactant for eosinophils.

    With regard to dry eye disease, the chronic inflammatory response impacts nociceptors in the damaged dendritic space to initiate a sensation of pain. In turn, these receptors are stimulated after impairment due to a release of tachykinins such as Substance P and RNA-derived Calcitonine gene-related peptide (CGRP) to which they are sensitive.7

    For the cornea, these receptors are primarily chemical sensors, but they are interrelated to mechanical and thermal stimuli in reference to recalcitrant superficial keratopathy, increased pH levels, and elevated tear osmolarity.8,9

    Evidence of such involvement of neuromediation affecting the ocular surface has been growing in the last two decades, suggesting that neuropeptides released from sensory and autonomic sympathetic and parasympathetic nerves may influence the pathogenesis and progression of dry eye and other autoimmune diseases.10

    Consequently, the increased secretion of these compounds may lead to a widespread chronic inflammatory response in which the ocular surface reaches a breaking point, causing meibomian glandular structure to undergo some level of hyperkeratinization, dysregulation of tear production by the lacrimal gland, and mucin decompensation due to deficient conjunctival goblet cells.11-13

    Switching gears to allergic conjunctivitis, the hallmark inflammatory response is a delayed Type IV hypersensitivity. Diving deeper into the ocular surface mucosa, both mucin-secreting goblet cells and a fine network of sensory nerve terminals are found in allergic diseases such as seasonal or perennial allergic conjunctivitis (SAC and PAC), atopic (AKC), and vernal keratoconjunctivitis (VKC).14

    By virtue of an increase in mast cell and eosinophil infiltration of the mucosa, it has been reported that Substance P levels are increased in the tears of patients with SAC compared with healthy individuals, suggesting that the compound may contribute to the pathogenesis and severity of allergic conjunctivitis.15

    With specific focus to the itching sensation, it is postulated that the peripheral nervous system could play a major role in its pathophysiology. With the symptom being triggered and maintained by stimulation of the nerve endings, inflammatory neuropeptides such as Substance P and calcitonin gene-related peptid (CGRP) foment the inflammatory cascade.16 A broadened molecular investigation of the neuropeptide effect is clearly required to gain a greater understanding of their involvement as to the presence, release, and specific roles played in ocular allergic reactions.

    Michael S. Cooper, OD
    Michael S. Cooper, OD, is in private practice in Willimantic, CT. He is a consultant to Allergan, BioTissue, Johnson & Johnson Vision ...


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