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

Pooja Khamar; Archana Padmanabhan Nair; Rohit Shetty; Tanuja Vaidya; Murali Subramani; Murugeswari Ponnalagu; Kamesh Dhamodaran; Sharon D'souza; Anuprita Ghosh; Natasha Pahuja; Rashmi Deshmukh; Prerna Ahuja; Kanchan Sainani; Rudy M. M. A. Nuijts; Debashish Das; Arkasubhra Ghosh; Swaminathan Sethu

doi:10.1167/iovs.19-26914

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

Pooja Khamar, Archana Padmanabhan Nair, Rohit Shetty, Tanuja Vaidya, Murali Subramani, Murugeswari Ponnalagu, Kamesh Dhamodaran, Sharon D'souza, Anuprita Ghosh, Natasha Pahuja, Rashmi Deshmukh, Prerna Ahuja, Kanchan Sainani, Rudy M. M. A. Nuijts, Debashish Das, Arkasubhra Ghosh^*, Swaminathan Sethu^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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 tear-soluble 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-1 beta, 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.

Original language	English
Pages (from-to)	2532-2542
Number of pages	11
Journal	Investigative Ophthalmology & Visual Science
Volume	60
Issue number	7
DOIs	https://doi.org/10.1167/iovs.19-26914
Publication status	Published - Jun 2019

Keywords

dry eye disease
corneal dendritic cells
nociception
inflammation
vitamin D
INTERLEUKIN-2 GENE-THERAPY
NEUROPEPTIDE-Y
D DEFICIENCY
PAIN
RECEPTOR
DISEASE
SUPPLEMENTATION
ANTINOCICEPTION
EPIDEMIOLOGY
MECHANISMS

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Khamar, P., Nair, A. P., Shetty, R., Vaidya, T., Subramani, M., Ponnalagu, M., Dhamodaran, K., D'souza, S., Ghosh, A., Pahuja, N., Deshmukh, R., Ahuja, P., Sainani, K., Nuijts, R. M. M. A., Das, D., Ghosh, A., & Sethu, S. (2019). Dysregulated Tear Fluid Nociception-Associated Factors, Corneal Dendritic Cell Density, and Vitamin D Levels in Evaporative Dry Eye. Investigative Ophthalmology & Visual Science, 60(7), 2532-2542. https://doi.org/10.1167/iovs.19-26914

@article{0f7cdab4ac294a37a2527b538be67db9,

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

abstract = "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 tear-soluble 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-1 beta, 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.",

keywords = "dry eye disease, corneal dendritic cells, nociception, inflammation, vitamin D, INTERLEUKIN-2 GENE-THERAPY, NEUROPEPTIDE-Y, D DEFICIENCY, PAIN, RECEPTOR, DISEASE, SUPPLEMENTATION, ANTINOCICEPTION, EPIDEMIOLOGY, MECHANISMS",

author = "Pooja Khamar and Nair, {Archana Padmanabhan} and Rohit Shetty and Tanuja Vaidya and Murali Subramani and Murugeswari Ponnalagu and Kamesh Dhamodaran and Sharon D'souza and Anuprita Ghosh and Natasha Pahuja and Rashmi Deshmukh and Prerna Ahuja and Kanchan Sainani and Nuijts, {Rudy M. M. A.} and Debashish Das and Arkasubhra Ghosh and Swaminathan Sethu",

note = "Funding Information: Supported by an Early Career Research Award, DST-SERB, Government of India to SS. The funders had no role in study design, data collection, and analysis. Publisher Copyright: {\textcopyright} 2019, Association for Research in Vision and Ophthalmology Inc.. All rights reserved.",

year = "2019",

month = jun,

doi = "10.1167/iovs.19-26914",

language = "English",

volume = "60",

pages = "2532--2542",

journal = "Investigative Ophthalmology & Visual Science",

issn = "0146-0404",

publisher = "Association for Research in Vision and Ophthalmology",

number = "7",

}

Khamar, P, Nair, AP, Shetty, R, Vaidya, T, Subramani, M, Ponnalagu, M, Dhamodaran, K, D'souza, S, Ghosh, A, Pahuja, N, Deshmukh, R, Ahuja, P, Sainani, K, Nuijts, RMMA, Das, D, Ghosh, A & Sethu, S 2019, 'Dysregulated Tear Fluid Nociception-Associated Factors, Corneal Dendritic Cell Density, and Vitamin D Levels in Evaporative Dry Eye', Investigative Ophthalmology & Visual Science, vol. 60, no. 7, pp. 2532-2542. https://doi.org/10.1167/iovs.19-26914

TY - JOUR

T1 - Dysregulated Tear Fluid Nociception-Associated Factors, Corneal Dendritic Cell Density, and Vitamin D Levels in Evaporative Dry Eye

AU - Khamar, Pooja

AU - Nair, Archana Padmanabhan

AU - Shetty, Rohit

AU - Vaidya, Tanuja

AU - Subramani, Murali

AU - Ponnalagu, Murugeswari

AU - Dhamodaran, Kamesh

AU - D'souza, Sharon

AU - Ghosh, Anuprita

AU - Pahuja, Natasha

AU - Deshmukh, Rashmi

AU - Ahuja, Prerna

AU - Sainani, Kanchan

AU - Nuijts, Rudy M. M. A.

AU - Das, Debashish

AU - Ghosh, Arkasubhra

AU - Sethu, Swaminathan

N1 - Funding Information: Supported by an Early Career Research Award, DST-SERB, Government of India to SS. The funders had no role in study design, data collection, and analysis. Publisher Copyright: © 2019, Association for Research in Vision and Ophthalmology Inc.. All rights reserved.

PY - 2019/6

Y1 - 2019/6

N2 - 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 tear-soluble 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-1 beta, 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.

AB - 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 tear-soluble 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-1 beta, 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.

KW - dry eye disease

KW - corneal dendritic cells

KW - nociception

KW - inflammation

KW - vitamin D

KW - INTERLEUKIN-2 GENE-THERAPY

KW - NEUROPEPTIDE-Y

KW - D DEFICIENCY

KW - PAIN

KW - RECEPTOR

KW - DISEASE

KW - SUPPLEMENTATION

KW - ANTINOCICEPTION

KW - EPIDEMIOLOGY

KW - MECHANISMS

U2 - 10.1167/iovs.19-26914

DO - 10.1167/iovs.19-26914

M3 - Article

C2 - 31195410

SN - 0146-0404

VL - 60

SP - 2532

EP - 2542

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

IS - 7

ER -