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Ruchita Selot, Jagdeesh Naidu, Nimisha Kumar, Rohit Shetty, Rajiv R Mohan, Arkasubhra Ghosh, Swaminathan Sethu; Increased expression of Retinoic acid-related Orphan Receptor gamma transcription factor and its products in keratoconus patients. Invest. Ophthalmol. Vis. Sci. 2018;59(9):744.
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© ARVO (1962-2015); The Authors (2016-present)
Keratoconus (KC) is an inflammatory corneal ectatic disease. IL-17 family of cytokines are reported to be increased in the tears of KC patients. Hence, levels of the transcription factor Retinoic acid-related Orphan Receptor gamma (RORg) and its isoform RORgT were evaluated in KC corneal epithelium.
The study was approved by the institutional ethics committee and samples were collected after written, informed consent. The corneal epithelium from non-KC controls (n=12, patients undergoing refractive correction by PRK) and KC patients (n=17, patients undergoing collagen cross-linking) were collected after written informed consent. In addition, epithelium from the 4mm ectatic zone (cone centered, based on topography) and non-ectatic zone (periphery) from KC patients (n=10) were also collected and stored at -80°C until further use. The corneal epithelium collection was performed without any deviation from standard of care. The mRNA expressions of RORg, RORgT and MMP9 were measured using quantitative PCR. Tear fluid IL-17A, IL-17F and IL-21 levels were measured by cytokine bead array.
Significantly higher expression of RORg (P<0.01) and RORgT (P<0.01) was observed in corneal epithelium from KC patients compared to healthy controls. Furthermore, the levels of RORgT was higher than RORg in KC based on the ratio of the normalized expression (RORg/RORgT). Increased trend in the expression of RORg and RORgT was observed in the cone (ectatic zone) compared to periphery (non-ectatic zone) epithelium of the same KC subjects. Furthermore, a positive correlation (r = 0.0669; p = 0.003) was observed between the RORgT and MMP9 expression in KC corneal epithelium. Higher levels of IL-17A, IL-17F and IL-21 were observed in the tear fluid of KC patients compared to controls.
Increased expression of RORg/RORgT in corneal epithelium in KC patients implicates its role in KC pathogenesis. Hence, this work suggests the possibility of targeting RORg/RORgT in the management of keratoconus.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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