Platelet-derived growth factor (PDGF)-C inhibits neuroretinal apoptosis in a murine model of focal retinal degeneration.

Abstract

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.

• Authors: Yujuan Wang, Mones S Abu-Asab, Cheng-Rong Yu, Zhongshu Tang, Defen Shen, Jingsheng Tuo, Xuri Li, Chi-Chao Chan
• Journal: Laboratory investigation; a journal of technical methods and pathology (Lab Invest) Vol. 94 Issue 6 Pg. 674-82 (Jun 2014) ISSN: 1530-0307 [Electronic] United States
• PMID: 24709779 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Lymphokines
• Platelet-Derived Growth Factor
• platelet-derived growth factor C

Topics

• Animals
• Apoptosis (drug effects)
• Lymphokines (analysis, genetics, metabolism, pharmacology)
• Mice
• Mice, Knockout
• Neovascularization, Pathologic
• Platelet-Derived Growth Factor (analysis, genetics, metabolism, pharmacology)
• Retina (drug effects, pathology)
• Retinal Degeneration (genetics, metabolism, pathology)