Impact modified glial-derived neurotrophic factor (GDNF) for regeneration of epithelial and epithelial-stromal corneal defect in the experiment



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Abstract

Objective is to study the effect of modified glial-derived neurotrophic factor (GDNF) on healing of epithelial and epithelial-stromal corneal lesions in mice C57BL / 6J. After corneal damage the instillations of supernatant conditioned by HEK293 cells expressed GDNF gene construction without pre- and pro- sequences were produced. For control, a medium conditioned by not transfected cells was used. We assessed the area of corneal epithelial defect and corneal erosion rate, developing after the epithelial defect. The immunohistochemical study using antibodies against cytokeratin 5/18, c-Met, collagen IV, phospho-ERK1/2, phospho-JNK1/2, Ki67, Bcl2, GAP43, TIMR-1, TGF-p, Bax, and MMP 9 was performed. The area of corneal epithelial defect in the eyes of experimental animals within one day after damage was smaller than in the control. Frequencies of corneal erosions formed in the eyes of experimental animals after damage was observed in 30-35% and 80-85% of cases in the experimental and control groups, respectively. Immunohistochemical studies using these antibodies showed that GDNF stimulated the proliferative activity of epithelial cells and keratinocytes, contributed to active migration and adhesion of epithelial cells, had anti-apoptotic and antifibrotic effects, took an active part in the formation of stromal nerve plexus. The results indicate the hopefulness of therapeutic application of the modified GDNF after corneal injury and the need for further research to develop and test methods for the therapeutic use of drugs on the basis of this neurotrophic factor.

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About the authors

N. A Gavrilova

A.I. Evdokimov Moscow State University of Medicine and Dentistry

Moscow, Russia

A. V Revischin

Institute of Gene Biology of RAS

Moscow, Russia

S. A Borzenok

S.N. Fedorov Eye Microsurgery Interdisciplinary Science and Technology Complex; S.N. Fedorov Eye Microsurgery Interdisciplinary Science and Technology Complex

Moscow, Russia

O. J Komova

A.I. Evdokimov Moscow State University of Medicine and Dentistry

Moscow, Russia

M. B Agammedov

A.I. Evdokimov Moscow State University of Medicine and Dentistry

Moscow, Russia

H. D Tonaeva

S.N. Fedorov Eye Microsurgery Interdisciplinary Science and Technology Complex

Moscow, Russia

D. S Ostrovsky

S.N. Fedorov Eye Microsurgery Interdisciplinary Science and Technology Complex

Moscow, Russia

G. V Pavlova

Institute of Gene Biology of RAS

Moscow, Russia

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