Tear film and ocular surface neuropeptides: Characteristics, synthesis, signaling and implications for ocular surface and systemic diseases

Asiedu, Kofi; Markoulli, Maria; Bombardieri, Stefano; Bron, Anthony J.; Doğru, Murat; Kwai, Natalie; Poynten, Ann M.; Willcox, Mark; Krishnan, Arun V.

doi:10.1016/j.exer.2022.108973

Cited by 19 publications

(12 citation statements)

References 151 publications

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“…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. 36,37 These findings imply that corneal nerve loss in type 2 diabetes mellitus may not be accompanied by significant neuroinflammation. Ocular surface inflammation is central to the pathogenesis of dry eye disease and ocular surface discomfort.…”

Section: Discussionmentioning

confidence: 84%

“…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 47,48 …”

Section: Discussionmentioning

confidence: 99%

“…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. 47,48 In diabetes, hyperglycemia instigates conjunctival microvessel leakage of glucose into the tear fluid, increasing the osmolarity of tears.…”

Section: Discussionmentioning

confidence: 99%

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

Asiedu¹,

Dhanapalaratnam

Krishnan

et al. 2022

Optom Vis Sci

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SIGNIFICANCEThere is a reduction in corneal nerve fiber density and length in type 2 diabetes mellitus with chronic kidney disease compared with type 2 diabetes mellitus alone; however, this difference does not result in worse ocular surface discomfort or dry eye disease.PURPOSEThis study aimed to determine the clinical impact of corneal nerve loss on ocular surface discomfort and markers of ocular surface homeostasis in people with type 2 diabetes mellitus without chronic kidney disease (T2DM–no CKD) and those with type 2 diabetes mellitus with concurrent chronic kidney disease (T2DM-CKD).METHODSParticipants were classified based on estimated glomerular filtration rates into two groups: T2DM-CKD (n = 27) and T2DM–no CKD (n = 28).RESULTSThere was a significant difference between the T2DM-CKD and T2DM–no CKD groups in corneal nerve fiber density (14.9 ± 8.6 and 21.1 ± 7.1 no./mm2, respectively; P = .005) and corneal nerve fiber length (10.0 ± 4.6 and 12.3 ± 3.7 mm/mm2, respectively; P = .04). Fluorescein tear breakup time was significantly reduced in T2DM-CKD compared with T2DM–no CKD (8.1 ± 4.4 and 10.7 ± 3.8 seconds, respectively; P = .01), whereas ocular surface staining was not significantly different (3.5 ± 1.7 and 2.7 ± 2.3 scores, respectively;P = .12). In terms of ocular surface discomfort, there were no significant differences in the ocular discomfort score scores (12.5 ± 11.1 and 13.6 ± 12.1, respectively; P = .81) and Ocular Pain Assessment Survey scores (3.3 ± 5.4 and 4.3 ± 6.1, respectively; P = .37) between the T2DM-CKD and T2DM–no CKD.CONCLUSIONSThe current study demonstrated that corneal nerve loss is greater in T2DM-CKD than in T2DM–no CKD. However, these changes do not impact ocular surface discomfort or markers of ocular surface homeostasis.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Asiedu¹,

Dhanapalaratnam

Krishnan

et al. 2022

Optom Vis Sci

Self Cite

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“…The eye and especially the tear film have become, in recent years, the target for researchers of being an outstanding source of biomarkers for the diagnosis of both ocular and systemic diseases such as dry eye, Sjogren's syndrome, keratoconus, cancer, and COVID-19 (47)(48)(49)(50)(51)(52). The main reason for this is that tears are the most accessible corporal fluid, and collecting them is easier, faster, and less invasive than the collection methods of other fluids (53).…”

Section: Eye As a Source Of Diagnostic Biomarkersmentioning

confidence: 99%

Presbyopia: An outstanding and global opportunity for early detection of pre-frailty and frailty states

Crooke

Martínez-Alberquilla²,

Madrid-Costa³

et al. 2022

Front. Med.

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“…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].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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The autonomic nervous system plays a crucial role in the maintenance of homeostasis. Neurogenic inflammation due to decreased stability of tear film may induce changes in autonomic nerve activity, which could be associated with symptom expression.This study aimed to measure biological parameters that represent autonomic nerve activity in dry eye (DE)s caused by tear film dysfunction and investigate their relationship with symptom intensity. This prospective, cross-sectional, comparative study evaluated 34 eyes of 34 participants (mean age: 52.5 ± 13.4 years; range: 20–81 years) without keratoconjunctival damage. Nineteen eyes in the DE group showed DE symptoms and tear break-up time (TBUT) of ≤5 seconds (short TBUT DE); the 15 eyes in the non-DE group showed no DE symptoms. Autonomic nerve activity was measured for 10 minutes—starting and ending 5 minutes before and after instilling ophthalmic solution—and evaluated using the low-frequency component (LF) to the high-frequency component (HF) ratio of heart rate variability (autonomic balance). The pre-ophthalmic solution administration LF/HF ratio was not significantly different (P = 0.59) between the two groups, however, the standard deviation of the LF/HF ratio (LF/HF-SD) tended to be higher in the DE group than that in the non-DE group (P = 0.086). The DE symptom intensity was significantly related to LF/HF-SD (P = 0.005), which significantly decreased after ophthalmic solution administration in the DE group (P = 0.04). The large fluctuations in autonomic balance may be key for the understanding of the mechanism underlying DE symptoms.

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Tear film and ocular surface neuropeptides: Characteristics, synthesis, signaling and implications for ocular surface and systemic diseases

Cited by 19 publications

References 151 publications

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

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

Presbyopia: An outstanding and global opportunity for early detection of pre-frailty and frailty states

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

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