The Role of Neuropeptides in Pathogenesis of Dry Eye

Abstract

Neuropeptides are known as important mediators between the nervous and immune systems. Recently, the role of the corneal nerve in the pathogenesis of various ocular surface diseases, including dry eye disease, has been highlighted. Neuropeptides are thought to be important factors in the pathogenesis of dry eye disease, as suggested by the well-known role between the nervous and immune systems, and several recently published studies have elucidated the previously unknown pathogenic mechanisms involved in the role of the neuropeptides secreted from the corneal nerves in dry eye disease. Here, we reviewed the emerging concept of neurogenic inflammation as one of the pathogenic mechanisms of dry eye disease, the recent results of related studies, and the direction of future research.

Novel Treatments for Chronic Ocular Surface Pain

“…24 Furthermore, nerves themselves may be a source of inflammation (eg, neurogenic inflammation) by the excessive or prolonged release of neuropeptides, such as substance P, calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY). 24…”

“…23 Moreover, an inflammatory response may be elicited by the interaction between immune cells (mast cells, macrophages, eosinophils, and lymphocytes) and sensory nerve endings responding to external stimuli. 24 Furthermore, nerves themselves may be a source of inflammation (eg, neurogenic inflammation) by the excessive or prolonged release of neuropeptides, such as substance P, calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY). 24 Currently, topical therapies such as cyclosporine A (CsA), lifitegrast, and corticosteroids have been used to target inflammation.…”

“…24 Furthermore, nerves themselves may be a source of inflammation (eg, neurogenic inflammation) by the excessive or prolonged release of neuropeptides, such as substance P, calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY). 24 Currently, topical therapies such as cyclosporine A (CsA), lifitegrast, and corticosteroids have been used to target inflammation. CsA is a calcineurin inhibitor that regulates T-cell activation, migration, and release of inflammatory cytokines.…”

Activity-Dependent Neuroprotective Protein (ADNP): An Overview of Its Role in the Eye

“…It is worth noting that a subpicomolar concentration of PACAP stimulated ADNP expression mainly through the MAPK signaling pathway and cAMP-dependent protein kinase activation [ 6 ]. Both VIP and PACAP showed important protective effects against different ocular diseases [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. The therapeutic use of PACAP or VIP presents some limitations, due to their short half-life caused by rapid enzymatic degradation [ 18 , 19 ].…”

Variability of autonomic nerve activity in dry eye with decreased tear stability

“…The Dry Eye Workshop II identified neuropathy as one of the etiologies of DE disease [10]. Neuropathic pain due to neurogenic inflammation caused by damage or irritation to sensory nerve endings on the ocular surface has been implicated as an important cause of DE symptoms [11][12][13][14]. Several studies on corneal sensory nerves related to neuropathic pain have focused on transient receptor potential vanilloid 1 (TRPV1), which is associated with pain sensation, and transient receptor potential melastatin 8 (TRPM8), which is associated with temperature change sensation on the corneal surface [15].…”