The Role Of PDGF-C In The Failure Of Anti-VEGF Treatment And Research Of Its Possibilty In The Treament In Neovascular Diseases

Purpose: To investigate whether PDGF-C may account for some of resistance,and whether PDGF-C may become a new therapeutic target of anti-angiogenesis therapies. Methods: In vivo: 1. To utilize laser-induced choroidal neovascularization (CNV) model using different mice strains, (1) Control group:normal mice, (2) Experimental group: laser-induced CNV mice, the eyes were harvested at 3d after laser treatment, tested the expression of PDGF-C in retinal and choroid. 2. To utilize laser-induced CNV model using C57BL/6 mice, (1)Control group: normal mice, (2) Experimental group: laser-induced CNV mice, the eyes were harvested at 3?7?14d after laser treatment, tested the expression of PDGF-C and PDGFRs in retinal and choroid. 3. To utilize laser-induced CNV model using C57BL/6 mice, ( 1 ) Control group: Intravitreal injections of nonspecific IgG antibody (5?g/eye) were performed immediately after laser treatment, (2) Experimental group: Intravitreal injections of VEGF nab (5?g/eye).4d later, tested the expression of PDGF-C and PDGFRs in retinal and choroid. 4.To utilize laser-induced CNV model using C57BL/6 mice, (1) Control group:Intravitreal injections of nonspecific IgG antibody (5?g/eye) were performed immediately after laser treatment, (2) Experimental group: Intravitreal injections of VEGF nab (5?g/eye), PDGF-C nab (5?g/eye) or VEGF nab (5?g/eye) together with PDGF-C nab (5?g/eye). The second intravitreal injection was performed 3d after. 7d later, harvested eyes for whole-mount choroid IB4 staining and imaging.5. To utilize laser-induced CNV model using C57BL/6 mice, ( 1) Control group:Intravitreal injections of nonspecific IgG antibody(0.7?g/eye) were performed immediately after laser treatment, (2) Experimental group: Intravitreal injections of VEGF nab (0.7?g/eye),PDGF-C nab (0.7?g/eye) or VEGF nab (0.7?g/eye)together with PDGF-C nab (0.7?g/eye). The second intravitreal injection was performed 3d after. 7d later, harvested eyes for whole-mount choroid IB4 staining and imaging. In vitro,(1) Control group: RAW 264.7?ARPE-19?HREC were cultured in serum-free medium adding nonspecific IgG antibody, 24h and 48h later,tested the expression of PDGF-C. (2) Experimental group: The same cells were cultured in serum-free medium adding VEGF nab, 24h and 48h later, tested the expression of PDGF-C. Result: (1) In certain mouse lines, the expression of PDGF-CC were upregulated after laser-treatment. (2) Inhibition of VEGF induced PDGF-CC expression. (3) Inhibition of both VEGF-A and PDGF-CC simultaneously reduced laser-induced CNV to a greater extent. Conclusions:PDGF-C may account for some of resistance, and PDGF-C may become a new therapeutic target of anti-angiogenesis therapies.