Dysregulated Tear Fluid Nociception-Associated Factors, Corneal Dendritic Cell Density, and Vitamin D Levels in Evaporative Dry Eye

Abstract

Citation: Khamar P, Nair AP, Shetty R, et al. Dysregulated tear fluid nociception-associated factors, corneal dendritic cell density, and vitamin D levels in evaporative dry eye. Invest Ophthalmol Vis Sci. 2019;60:2532-2542. https://doi.org/10.1167 PURPOSE. The purpose of this study was to study the status and association among tear-soluble factors, corneal dendritic cell density, vitamin D, and signs and symptoms in dry eye disease (DED). METHODS.A total of 33 control subjects and 47 evaporative dry eye patients were included in the study. DED diagnosis and classification was based on the 2017 Report of the Tear Film & Ocular Surface Society International Dry Eye Workshop (TFOS DEWS II). DED workup, including tear film break-up time (TBUT), Schirmer's test I (STI), corneal and conjunctival staining, ocular surface disease index (OSDI) scoring, and in vivo confocal microscopy (to assess corneal dendritic cell density [cDCD] and subbasal nerve plexus [SBNP] features) was performed in the study subjects. Tear fluid using Schirmer's strip and serum were collected from the subjects. Multiplex ELISA or single analyte ELISA was performed to measure 34 tearsoluble factors levels including vitamin D.RESULTS. Significantly higher OSDI discomfort score, lower TBUT, and lower STI were observed in DED patients. cDCD was significantly higher in DED patients. No significant difference was observed in SBNP features. Tear fluid IL-1b, IL-17A, MMP9, MMP10, MMP9/ TIMP ratio, and VEGF-B were significantly higher in DED patients. Significantly lower tear fluid IL-2, IP-10, NPY, VEGF-A, and vitamin D was observed in DED patients. These dysregulated tear factors showed significant associations with DED signs and symptoms.CONCLUSIONS. Altered tear fluid soluble factors with potential to modulate nociception exhibited a distinct association with ocular surface discomfort status, TBUT, STI, and cDCD. This implies a functional relationship between the various tear-soluble factors and dry eye pathogenesis, indicating new molecular targets for designing targeted therapies.

Genistein‐Calcitriol Mitigates Hyperosmotic Stress‐Induced TonEBP, CFTR Dysfunction, VDR Degradation and Inflammation in Dry Eye Disease

“…Although a discordance in the association between reduced serum vitamin D levels and DED signs and symptoms was reported, 29,30,46 we had shown that the tear film levels rather than serum vitamin D levels exhibited stronger association with DED signs and symptoms. 9 To further the concept of investigating the local status of vitamin D homeostasis, we investigated the levels of VDR in patients with DED. VDR mediates the cellular response induced by vitamin D and absence of VDR increased basal level of inflammation, rendering cells more susceptible to stress.…”

“…24,25 A number of studies report the association of vitamin D levels, including tear vitamin D and DED along with the restoration of tear film osmolarity following vitamin D supplementation. 9,[26][27][28] However, there has also been contradicting studies regarding the relationship between serum vitamin D levels and DED signs and symptoms. 29,30 These studies suggest an unexplored possibility of dysregulated VDR expression or function, in addition to lower vitamin D levels, in DED.…”

Food Supplements in the Treatment of Ophthalmic Diseases: Preclinical and Clinical Studies

“…They found that decreased serum vitamin D was significantly associated with higher levels of inflammatory interleukin IL-17A/F, interferon-γ, monocyte chemotactic protein 1, intercellular adhesion molecule 1, IL-4, IL-10, and decreased levels of antinflammatory IL-2 in tears of dry eye patients in comparison to healthy controls [241]. Altered tear fluid soluble factors with potential to modulate nociception exhibited a distinct association with the ocular surface discomfort status [242]. Vitamin D deficiency was found to be associated with neuralgia and chronic pain.…”

“…In a case report it was observed that a vitamin D-deficient patient with corneal neuralgia had relief from burning sensation and pain by vitamin D supplementation, 1,000 IU/day, while topical therapies and lubricants were not effective [243]. It is thus probable that low vitamin D could contribute to the severity of ocular surface symptoms either by directly influencing nociceptive mechanisms or by affecting the presence of inflammatory cytokines [235,236,241,242]. Khamar et al, reported the dysregulation of tear fluid nociception-associated factors, corneal dendritic cell density, and vitamin D levels in dry eye patients.…”

Detection of amyloid-beta and tau in tear fluid of patients with Alzheimer’s disease

“…Before storage at -80 °C, the tear migration length (a marker for tear volume) was recorded. Tear uid was extracted from the Schirmer strip by agitating small cut pieces of these strips in 60 µL PBS, Tween20 0.5% and cOmplete™ Protease Inhibitor Cocktail (Roche, Basel, Switzerland) at 4 °C for 1.5 hours (16,17). Tear uid was then eluted by centrifugation and stored at -80 °C until further use.…”