Corneal Vascular Membrane Epithelial Cell Phenotype Identification And Neovascularization Target Screening

Purpose:To determine the epithelial lineage of origin in corneal pannus tissue surgically removed from patients with total limbal stem cell deficiency. To search and explore the role of related angiogenic factors in the angiogenesis process of corneal neovascularization induced by different etiological factors. To explore the possible mechanism of different clinical effectiveness of VEGF inhibitors in the fields of cornea.Methods:The lineage of origin of the entire pannus removed from 26 corneas were analyzed by immunohistochemistry and reverse transcription-polymerase chain reaction, respectively. Twenty-six eyes with profound corneal neovascularization were arised from chemical injury (13 eyes), thermal injury (8 eyes), trauma (3 eyes), ocular cicatricial pemphigoid (1 eye), and Stevens-Johnson syndrome (1 eye). Phenotypic analysis of the epithelium was performed by immunohistochemistry. And we searched and explored the role of related angiogenic factors in the angiogenesis process of corneal neovascularization by microarray, immunohistochemistry and reverse transcription polymerase chain reaction.Results:The expression of all markers (cytokeratin [CK] 3, CK12, CK7, CK19, and mucin 5AC) differed in healthy cornea and conjunctiva. Expression of lineage markers (CK3-, CK19+, P63+/-) was similar in pannus to conjunctiva, but not to cornea. We selected 15 angiogenic factors in 24 pannus with profound corneal neovascularization were arised from chemical injury (13 eyes), thermal injury (8 eyes), and trauma (3 eyes). PLXDC1, TGFB2, EREG, IL6, IL1β, TNFRSF12a, MMP2, FAP, NOTCH4, HEY2, and SFRP2 were involved in the process of corneal neovascularization in clinical pannus and neovascularized mouse cornea.Conclusions:Corneal neovascularization is characterized by ingrowth of abnormal inflamed tissue with a conjunctival phenotype. VEGF expression increased significantly in the acute phase of corneal neovascularization. Early treatment with bevacizumab seems to be beneficial in the management of corneal neovascularization in the acute phase of corneal neovascularization. The investigation of the relationship between the angiogenic factors and corneal NV may contribute to the search for novel targets for inhibiting corneal NV.