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 [Crb1rd8] (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.
Highlights
Platelet-derived growth factor (PDGF)-C is a PDGF family member.[1,2] It is a polypeptide of 345 amino acids with potent pleiotropic effects and functions as a homodimer, PDGF-CC.[3]
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
Fundoscopy revealed that PDGF-CCtreated eyes at 2 months had significant improvement over phosphate-buffered saline (PBS) controls, with fewer and smaller deep retinal lesions
Summary
Platelet-derived growth factor (PDGF)-C is a PDGF family member.[1,2] It is a polypeptide of 345 amino acids with potent pleiotropic effects and functions as a homodimer, PDGF-CC.[3]. Age-related macular degeneration (AMD) is a multifactorial neurodegenerative disease characterized by progressive degeneration of the photoreceptor/RPE complex primarily in the retinal macula It has become the major cause of irreversible central vision loss in the elderly worldwide.[19,20,21] As the photoreceptors and RPE are closely associated, a change in any single component of this complex could result in photoreceptor death.[22] Previous evidence reveals a link between photoreceptor degeneration and AMD.[23,24,25] Many clinical and experimental studies have linked AMD neurodegeneration to a variety of factors, including aging, oxidative stress, parainflammation, genetic predisposition, and environmental elements.[26,27,28,29,30,31,32] In certain conditions, the photoreceptor/RPE complex is exposed to numerous stimuli, such as oxidants, cytokines, and/or neurotoxins, which contribute to AMD pathogenesis.[33] In addition, studies have shown that apoptosis of RPE and photoreceptors has a vital role in geographic atrophy AMD.[34,35]
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