Involvement of SDF1a and STAT3 in granulocyte colony-stimulating factor rescues optic ischemia-induced retinal function loss by mobilizing hematopoietic stem cells.

نویسندگان

  • Po-Kang Lin
  • Chia-Ying Ke
  • Chin Ni Khor
  • Yu-Jyun Cai
  • Yih-Jing Lee
چکیده

PURPOSE Granulocyte colony-stimulating factor (G-CSF) has been applied clinically for several years. In this study, we used G-CSF to induce the mobilization of hematopoietic progenitor cells into peripheral blood in an ischemia-induced retinal degeneration model. METHODS Male Sprague-Dawley rats received G-CSF treatment for 5 days following optic ligation. Histologic and functional evaluations were performed and results were compared with those from untreated rats. Real-time PCR, Western blotting, and immunohistochemical analyses were used to evaluate the expression of retinal cell markers and other substances. RESULTS Retinal histology showed that transient optic ligation induced retinal cell loss. Postischemia, animals that received G-CSF treatment had a higher retinal cell survival rate than that of control animals. Analysis of apoptosis showed that retinas from G-CSF-treated animals exhibited fewer apoptotic cells than those from control retinas. Immunoblotting analyses indicated the presence of greater numbers of CD34-, but less chemokine receptor type 4 (CXCR4)-, and stromal cell-derived factor 1 alpha (SDF1α)-positive cells in the G-CSF-treated ischemic retinas than in ischemic retinas without treatment 14 days after ischemia. The ischemic retinas from G-CSF-treated animals displayed upregulated Thy1 and opsin expression compared with the retinas from untreated animals. Electroretinography indicated superior retinal function in animals treated with G-CSF than in untreated animals postischemia, and that STAT3 might play an important role. CONCLUSIONS Our results suggest that G-CSF reduces optic ischemia-induced retinal cell loss, possibly through STAT3-regulated mobilization of hematopoietic progenitor cells to the retina.

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عنوان ژورنال:
  • Investigative ophthalmology & visual science

دوره 54 3  شماره 

صفحات  -

تاریخ انتشار 2013