TY - JOUR
T1 - Keratoconus patients exhibit a distinct ocular surface immune cell and inflammatory profile
AU - D'Souza, S.
AU - Nair, A.P.
AU - Sahu, G.R.
AU - Vaidya, T.
AU - Shetty, R.
AU - Khamar, P.
AU - Mullick, R.
AU - Gupta, S.
AU - Dickman, M.M.
AU - Nuijts, R.M.M.A.
AU - Mohan, R.R.
AU - Ghosh, A.
AU - Sethu, S.
N1 - Funding Information:
This work was funded by Narayana Nethralaya Foundation, Bangalore, India. The funders had no role in study design, data collection, and analysis.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/10/22
Y1 - 2021/10/22
N2 - Inflammatory factors have been considered to contribute to keratoconus (KC) pathogenesis. This study aims to determine the immune cells subsets and soluble inflammatory factor profile on the ocular surface of KC patients. 32 KC subjects (51 eyes) across different grades of severity and 15 healthy controls (23 eyes) were included in the study. Keratometry and pachymetry measurements were recorded. Ocular surface immune cells (collected by ocular surface wash) immunophenotyped using flow cytometry include leukocytes, neutrophils, macrophages, natural killer (NK) cells, pan-T cells, gamma delta T (gamma delta T) cells and NKT cells. Tear fluid collected using Schirmer's strip was used to measure 50 soluble factors by multiplex ELISA. Proportions of activated neutrophils, NK cells and gamma delta T cells were significantly increased in KC patients. Significantly higher levels of tear fluid IL-1 beta, IL-6, LIF, IL-17A, TNF alpha, IFN alpha/beta/gamma, EPO, TGF beta 1, PDGF-BB, sVCAM, sL-selectin, granzyme-B, perforin, MMP2, sFasL and IgE, along with significantly lower levels of IL-1 alpha and IL-9 were observed in KC patients. Alterations observed in few of the immuno-inflammatory parameters correlated with grades of disease, allergy, eye rubbing and keratometry or pachymetry measurements. The observation implies a distinct immuno-inflammatory component in KC pathogenesis and its potential as an additional therapeutic target in KC management.
AB - Inflammatory factors have been considered to contribute to keratoconus (KC) pathogenesis. This study aims to determine the immune cells subsets and soluble inflammatory factor profile on the ocular surface of KC patients. 32 KC subjects (51 eyes) across different grades of severity and 15 healthy controls (23 eyes) were included in the study. Keratometry and pachymetry measurements were recorded. Ocular surface immune cells (collected by ocular surface wash) immunophenotyped using flow cytometry include leukocytes, neutrophils, macrophages, natural killer (NK) cells, pan-T cells, gamma delta T (gamma delta T) cells and NKT cells. Tear fluid collected using Schirmer's strip was used to measure 50 soluble factors by multiplex ELISA. Proportions of activated neutrophils, NK cells and gamma delta T cells were significantly increased in KC patients. Significantly higher levels of tear fluid IL-1 beta, IL-6, LIF, IL-17A, TNF alpha, IFN alpha/beta/gamma, EPO, TGF beta 1, PDGF-BB, sVCAM, sL-selectin, granzyme-B, perforin, MMP2, sFasL and IgE, along with significantly lower levels of IL-1 alpha and IL-9 were observed in KC patients. Alterations observed in few of the immuno-inflammatory parameters correlated with grades of disease, allergy, eye rubbing and keratometry or pachymetry measurements. The observation implies a distinct immuno-inflammatory component in KC pathogenesis and its potential as an additional therapeutic target in KC management.
KW - DELTA T-CELLS
KW - LYSYL OXIDASE
KW - EXTRACELLULAR-MATRIX
KW - TEAR FILM
KW - OXIDATIVE STRESS
KW - EXPRESSION
KW - COLLAGEN
KW - GAMMA
KW - MATRIX-METALLOPROTEINASE-9
KW - EPITHELIUM
U2 - 10.1038/s41598-021-99805-9
DO - 10.1038/s41598-021-99805-9
M3 - Article
C2 - 34686755
SN - 2045-2322
VL - 11
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 20891
ER -