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Expression of Lymphangiogenic Markers in Rejected Human Corneal Buttons after Penetrating Keratoplasty

 Yuri Seo  ;  Mee Kum Kim  ;  Joon H. Lee  ;  Eun-Ju Chang  ;  Eung Kweon Kim  ;  Hyung Keun Lee 
 CURRENT EYE RESEARCH, Vol.40(9) : 902-912, 2015 
Journal Title
Issue Date
Adult ; Aged ; Biomarkers/metabolism ; Cornea/metabolism* ; Cornea/pathology ; Female ; Gene Expression Regulation* ; Graft Rejection/genetics* ; Graft Rejection/metabolism ; Graft Rejection/pathology ; Humans ; Keratoplasty, Penetrating/adverse effects* ; Lymphangiogenesis/genetics* ; Male ; Microscopy, Confocal ; Middle Aged ; RNA/genetics* ; Real-Time Polymerase Chain Reaction ; Vascular Endothelial Growth Factors/biosynthesis ; Vascular Endothelial Growth Factors/genetics* ; Young Adult
Lymphangiogenesis ; VEGF ; VEGFR ; penetrating keratoplasty ; rejection
PURPOSE: To investigate the extent and distribution of lymphangiogenesis in the rejected corneal graft, we determined the expression of several lymphangiogenic markers in rejected human corneal buttons. MATERIAL AND METHODS: Thirty-four corneal buttons were obtained from patients who underwent re-keratoplasty for graft rejection after penetrating keratoplasty. All corneas showed signs of rejection, such as, sudden mutton-fat keratic precipitates (KPs) or lines before re-keratoplasty. The corneas were halved, and one half was used for immunostaining and the other half was used for RT-PCR. Expression of vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF-D, VEGFR-2, VEGFR-3, LYVE-1 and podoplanin were measured as lymphangiogenic markers. Four non-operated normal corneas were used as controls. RESULTS: Numerous podoplanin positive cells were found in the anterior and posterior stroma. However, LYVE-1 positive mature lymphatics were found only in herpetic keratitis (HK)-induced graft rejection, and not in pseudophakic bullous keratopathy (PBK). RT-PCR showed that levels of VEGF-A, VEGF-C, VEGFR-2, and VEGFR-3 mRNAs were elevated in rejected corneal buttons versus the non-operated control corneas. Based upon the pre-keratoplasty pathologic conditions, HK cases showed higher levels of VEGF-A and VEGFR-2 than PBK. The mRNA ratios (keratoplastic cornea/normal cornea) for VEGF-A and VEGFR-2 were 8.9 and 5.8, respectively. CONCLUSIONS: The results suggested that the VEGF-A and the VEGFR-2 may be a more important pathway for lymphangiogenesis in rejected corneal grafts than the VEGFR-3. In addition, organized lymphangiogenesis is more prominent in HK than PBK.
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1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Eung Kweon(김응권) ORCID logo https://orcid.org/0000-0002-1453-8042
Lee, Hyung Keun(이형근) ORCID logo https://orcid.org/0000-0002-1123-2136
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