Platelet-derived growth factor (PDGF)-C inhibits neuroretinal apoptosis in a murine model of focal retinal degeneration.
Platelet-derived growth factor (PDGF)-C is a member of the PDGF family and is critical for neuronal survival in the central nervous system. We studied the possible survival and antiapoptotic effects of PDGF-C on focal retinal lesions in Ccl2(-/-)/Cx3cr1(-/-) on C57BL/6N [Crb1(rd8)] (DKO rd8) background mice, a model for progressive and focal retinal degeneration. We found no difference in transcript and protein expression of PDGF-C in the retina between DKO rd8 mice and wild type (WT, C57BL/6N). Recombinant PDGF-CC protein (500 ng/eye) was injected intravitreally into the right eye of DKO rd8 mice with phosphate-buffered saline as controls into the left eye. The retinal effects of PDGF-C were assessed by fundoscopy, ocular histopathology, A2E levels, apoptotic molecule analysis, and direct flat mount retinal vascular labeling. We found that the PDGF-CC-treated eyes showed slower progression or attenuation of the focal retinal lesions, lesser photoreceptor and retinal pigment epithelial degeneration resulting in better-preserved photoreceptor structure. Lower expression of apoptotic molecules was detected in the PDGF-CC-treated eyes than in controls. In addition, no retinal neovascularization was observed after PDGF-CC treatment. Our results demonstrate that PDGF-C potently ameliorates photoreceptor degeneration via the suppression of apoptotic pathways without inducing retinal angiogenesis. The protective effects of PDGF-C suggest a novel alternative approach for potential age-related retinal degeneration treatment.
1] Immunopathology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA [2] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China.
Yujuan
Y
Wang
Histopathology Core, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Mones S
MS
Abu-Asab
Molecular Immunology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Cheng-Rong
CR
Yu
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China.
Zhongshu
Z
Tang
Immunopathology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Defen
D
Shen
Immunopathology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Jingsheng
J
Tuo
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China.
Xuri
X
Li
1] Immunopathology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA [2] Histopathology Core, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Chi-Chao
CC
Chan
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D008222:Lymphokines / Q000032:analysis / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic; D010982:Platelet-Derived Growth Factor / Q000032:analysis / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; C411423:platelet-derived growth factor C