Ocular Surface Ion-Channels Are Closely Related to Dry Eye: Key Research Focus on Innovative Drugs for Dry Eye

Abstract

Abundant ion-channels, including various perceptual receptors, chloride channels, purinergic receptor channels, and water channels that exist on the ocular surface, play an important role in the pathogenesis of dry eye. Channel-targeting activators or inhibitor compounds, which have shown positive effects in in vivo and in vitro experiments, have become the focus of the dry eye drug research and development, and individual compounds have been applied in clinical experimental treatment. This review summarized various types of ion-channels on the ocular surface related to dry eye, their basic functions, and spatial distribution, and discussed basic and clinical research results of various channel receptor regulatory compounds. Therefore, further elucidating the relationship between ion-channels and dry eye will warrant research of dry eye targeted drug therapy.

Impact of Peripheral and Corneal Neuropathy on Markers of Ocular Surface Discomfort in Diabetic Chronic Kidney Disease

“…Morphological changes measured with corneal confocal microscopy may not reflect corneal nerve neurophysiological abnormalities, which may play a predominant role in dry eye disease. 34,45 Furthermore, studies have shown that ocular surface inflammation or loss of homeostasis can induce neuropeptide production and secretion in large-sized trigeminal ganglion ocular surface neurons, supporting dysfunctional corneal nociceptors and not corneal nerve fiber loss as the mediator of dry eye disease in these two diabetes groups. 37,46 Also, nerve excitability studies have shown abnormalities in nerve conduction in type 2 diabetes mellitus with or without chronic kidney disease, suggesting the potential of corneal nerve dysfunction instead of nerve fiber loss as the driver of dry eye disease in type 2 diabetes mellitus.…”

“…Our study used corneal confocal microscopy, which provides corneal nerve morphological parameters rather than cornea neurophysiological measures such as nerve excitability. Morphological changes measured with corneal confocal microscopy may not reflect corneal nerve neurophysiological abnormalities, which may play a predominant role in dry eye disease 34,45 . Furthermore, studies have shown that ocular surface inflammation or loss of homeostasis can induce neuropeptide production and secretion in large-sized trigeminal ganglion ocular surface neurons, supporting dysfunctional corneal nociceptors and not corneal nerve fiber loss as the mediator of dry eye disease in these two diabetes groups 37,46 .…”

“…These findings suggest that other mechanisms may underlie the pathogenesis of dry eye disease in these two groups aside from corneal nerve loss. Studies have shown that the neurosensory abnormalities in dry eye are due to abnormal expression of ion channels and their functional abnormalities, hypersensitivity or injury to corneal nociceptors, and neuroinflammatory cascade via secretion of neuropeptides and other neuromediators 7,8,34 …”

“…Studies have shown that the neurosensory abnormalities in dry eye are due to abnormal expression of ion channels and their functional abnormalities, hypersensitivity or injury to corneal nociceptors, and neuroinflammatory cascade via secretion of neuropeptides and other neuromediators. 7,8,34 In laser-assisted in situ keratomileusis (LASIK), corneal nerve loss is associated with the severity of dry eye symptoms and clinical signs 35 ; however, corneal nerve loss in LASIK is quite different from type 2 diabetes mellitus. In LASIK, the corneal nerve loss is acute, and it is accompanied by an increased level of tear neuropeptides and neurotrophins, which instigate neuroinflammatory pathways; however, in type 2 diabetes mellitus, there is gradual loss of corneal nerve fibers, and no difference in tear neuropeptide level is noted between type 2 diabetes mellitus and healthy controls.…”

Moxibustion with Walnut Shell Spectacles Could Improve the Objective Symptoms and Tear Film Stability of Patients with Dry Eye Disease: A Randomized Controlled Trial

“…Currently, the most important method for treating DED is using artifcial tears locally to improve ocular surface humidity and lubrication capacity [38,39]. Some topical drugs are approved for treating DED with anti-infammatory and immunomodulatory efects, such as Cyclosporin A [40], corticosteroids [41], as well as emerging therapeutics such as lacrimal and diquafosol sodium [42][43][44][45][46]. Also, there are still challenges in the treatment of DED [47].…”