Photoreceptor rescue of pigment epithelium-derived factor-impregnated nanoparticles in Royal College of Surgeons rats

• Published in: Molecular vision 2012-12, Vol.18, p.3079-3086
• Main Authors: Akiyama, Goichi, Sakai, Tsutomu, Kuno, Noriyuki, Kimura, Erika, Okano, Kiichiro, Kohno, Hideo, Tsuneoka, Hiroshi
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Disease Models, Animal; Electroretinography; Eye Proteins - chemistry; Eye Proteins - pharmacology; Gene Expression; Immunohistochemistry; In Situ Nick-End Labeling; Intravitreal Injections; Iodine Radioisotopes; Male; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Nerve Growth Factors - chemistry; Nerve Growth Factors - pharmacology; Photoreceptor Cells, Vertebrate - drug effects; Photoreceptor Cells, Vertebrate - metabolism; Photoreceptor Cells, Vertebrate - pathology; Rats; Rats, Wistar; Retinal Degeneration - drug therapy; Retinal Degeneration - genetics; Retinal Degeneration - metabolism; Retinal Degeneration - pathology; Rod Opsins - genetics; Rod Opsins - metabolism; Serpins - chemistry; Serpins - pharmacology; Vitreous Body - metabolism; Vitreous Body - pathology
• ISSN: 1090-0535

To investigate the protective effect of intravitreal injection of pigment epithelium-derived factor-impregnated nanoparticles (PEDF-NPs) against photoreceptor degeneration in Royal College of Surgeons (RCS) rats. Three-week-old RCS rats received an intravitreal injection of PBS, blank NPs, PEDF (2.5 μg), or PEDF-NPs (2.5 μg). Eyes were assessed with morphological, immunohistochemical, and physiologic analysis over the following 8 weeks. Cell death was examined using the terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling (TUNEL) assay. In RCS rats, the a- and b-wave amplitudes on electroretinograms in eyes treated with PEDF-NPs were greater than those in retinas receiving other treatment. Immunocytochemistry showed consistently greater opsin preservation in eyes treated with PEDF-NPs. A significantly higher number of photoreceptors and significantly fewer TUNEL-positive cells were present after treatment with PEDF-NPs, compared to PEDF-treated eyes. The results suggest that intravitreally injected PEDF-NPs delayed photoreceptor degeneration by inhibiting apoptosis in the RCS rat retina due to targeting and sustained release of PEDF.