Identification of novel predictive factors for post surgical corneal haze
| Autor: | Rajani Kanth Vangala, Naren Shetty, Anuprita Ghosh, Vishal Jhanji, Nimisha R Kumar, Arkasubhra Ghosh, V. G. Abilash, Ankit Sharma, Rohit Shetty, Rajiv R. Mohan, Natasha Pahuja, Pooja Khamar |
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| Přispěvatelé: | Oogheelkunde, RS: MHeNs - R3 - Neuroscience |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male MYOFIBROBLAST Haze genetic structures medicine.medical_treatment lcsh:Medicine Cohort Studies 0302 clinical medicine Corneal Opacity Postoperative Complications Fibrosis Cell Movement Risk Factors Refractive surgery PHOTOREFRACTIVE KERATECTOMY Myopia Guanine Nucleotide Exchange Factors FIBROSIS lcsh:Science Corneal epithelium GENE-EXPRESSION Multidisciplinary Epithelium Corneal EPITHELIAL-CELLS TGF-BETA Prognosis Photorefractive keratectomy medicine.anatomical_structure Female RNA Interference Signal Transduction Adult medicine.medical_specialty Corneal diseases MITOMYCIN-C Article Cell Line 03 medical and health sciences Young Adult Ophthalmology TGF beta signaling pathway medicine Humans Genetic Predisposition to Disease REFRACTIVE SURGERY Wound Healing Corneal Haze business.industry GROWTH-FACTOR-BETA Gene Expression Profiling lcsh:R medicine.disease eye diseases 030104 developmental biology STROMAL CELLS 030221 ophthalmology & optometry lcsh:Q sense organs Wound healing business Biomarkers |
| Zdroj: | Scientific Reports, Vol 9, Iss 1, Pp 1-14 (2019) Scientific Reports Scientific Reports, 9:16980. Nature Publishing Group |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-019-53123-3 |
| Popis: | Molecular factors altered in corneas that develop haze post refractive surgery have been described, but pre-existing factors that predispose clinically normal corneas to aberrant fibrosis post surgery and the role of the corneal epithelium remains unknown. We analyzed the global gene expression in epithelium collected intraoperatively from subjects undergoing photorefractive keratectomy. Subjects were grouped into those that developed haze 12 months post surgery (n = 6 eyes; haze predisposed) and those that did not develop haze in a similar follow up duration (n = 11 eyes; controls). Ontological analysis of 1100 upregulated and 1780 downregulated genes in the haze predisposed group revealed alterations in pathways associated with inflammation, wnt signaling, oxidative stress, nerve functions and extra cellular matrix remodeling. Novel factors such as PREX1, WNT3A, SOX17, GABRA1and PXDN were found to be significantly altered in haze predisposed subjects and those with active haze(n = 3), indicating their pro-fibrotic role. PREX1 was significantly upregulated in haze predisposed subjects. Ectopic expression of PREX1 in cultured human corneal epithelial cells enhanced their rate of wound healing while its ablation using shRNA reduced healing compared to matched controls. Recombinant TGFβ treatment in PREX1 overexpressing corneal cells led to enhanced αSMA expression and Vimentin phosphorylation while the converse was true for shPREX1 expressing cells. Our data identify a few novel factors in the corneal epithelium that may define a patient’s risk to developing post refractive corneal haze. |
| Databáze: | OpenAIRE |
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