Identification of novel predictive factors for post surgical corneal haze

Nimisha R. Kumar, Pooja Khamar, Rohit Shetty, Ankit Sharma, Naren Shetty, Natasha Pahuja, Valsala Gopalakrishnan Abilash, Vishal Jhanji, Anuprita Ghosh, Rajiv R. Mohan, Rajani Kanth Vangala, Arkasubhra Ghosh*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 TGF beta treatment in PREX1 overexpressing corneal cells led to enhanced alpha SMA 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.

Original languageEnglish
Article number16980
Number of pages14
JournalScientific Reports
Volume9
DOIs
Publication statusPublished - 18 Nov 2019

Keywords

  • GROWTH-FACTOR-BETA
  • PHOTOREFRACTIVE KERATECTOMY
  • GENE-EXPRESSION
  • REFRACTIVE SURGERY
  • EPITHELIAL-CELLS
  • STROMAL CELLS
  • MITOMYCIN-C
  • TGF-BETA
  • FIBROSIS
  • MYOFIBROBLAST

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