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Limbal epithelial stem-microenvironmental alteration leads to pterygium development

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Abstract

Maintenance of tissue homeostasis relies on the accurate regulation of tissue specific stem cell activity which is governed by the dynamic interaction between the positive and negative feedback modulating mechanism of stem cell microenvironmental niche. Alteration or deregulation of the “stem-microenvironmental networking” provokes disease development. Limbal epithelial stem cells (LESC) are the initiator hierarchy that maintains corneal integrity. Compartmentalization of LESC within the limbal vicinity provides an opportunity to understand the stem-microenvironmental relationship. The purpose of this study was to determine the microenvironmental alteration associated with LESCs fate in pterygium condition in comparison with healthy state. Clinical observations evaluated the ocular surface disorder with respect to corneal vascularization, tear film abnormality, and thickening of limbal area in pterygium patients. Structural alteration of limbal stem/progenitor cells and its neighboring niche components were observed using histology and scanning electron microscopy. Receptor overexpression of TGFβ-R1, EGF-R1, and IL6-Rα and alteration of IL2-Rα expression pointed toward aberration of “stem-microenvironmental networking” in the limbal vicinity during disease development. Increased cell proliferation index along with TERT, Cyclin-D1, and PCNA over-expression in limbal part of pterygium epithelial cells indicated increased cellular proliferation and disturbed homeostatic equilibrium. We postulate that pterygium is associated with limbal microenvironmental anomaly where the resident epithelial cells became hyperproliferative.

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Abbreviations

LESC:

Limbal epithelial stem cells

UV-B:

Ultra violet-B

TGFβ-R1:

Transforming growth factor beta-receptor 1

EGF-R1:

Epidermal growth factor-receptor 1

IL6-Rα:

Interleukin 6- Receptor alpha

TERT:

Telomerase reverse transcriptase

PCNA:

Proliferating cell nuclear antigen

AS-OCT:

Anterior segment optical coherence tomography

PCC:

Peripheral corneal thickness

CCT:

Central corneal thickness

SEM:

Scanning electron microscopy

PI:

Proliferation index

LESCDD:

Limbal stem cell deficiency diseases

EMT:

Epithelial–mesenchymal transition

MAPK:

Mitogen activated protein kinase

gp130:

Glycoprotein 130

FBS:

Fetal bovine serum

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Acknowledgement

We are thankful to the Indian Council of Medical Research (ICMR) for their sponsorship, The Director, Calcutta School of Tropical Medicine (CSTM), The Director, Regional Institute of Ophthalmology (RIO) Kolkata and The West Bengal University of Health Sciences (WBUHS) for the facilities provided. This work was supported by Indian Council of Medical Research (80/10/2008/BMS/Stem cell).

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Authors indicate no potential conflicts of interest.

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  1. Stem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, 108 C R Avenue, Kolkata, 700073, India

    Prosun Das, Arjun Gokani, Ketaki Bagchi, Gautam Bhaduri, Samaresh Chaudhuri & Sujata Law

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  1. Prosun Das
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  2. Arjun Gokani
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Das, P., Gokani, A., Bagchi, K. et al. Limbal epithelial stem-microenvironmental alteration leads to pterygium development. Mol Cell Biochem 402, 123–139 (2015). https://doi.org/10.1007/s11010-014-2320-z

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