Protection of photoreceptor cells from phototoxicity by transplanted retinal pigment epithelial cells expressing different neurotrophic factors.
Transplantation of cells or tissues and the intravitreal injection of neurotrophic factors are two methods that have been used to treat retinal diseases. The purpose of this study was to examine the effects of combining both methods: the transplantation of retinal pigment epithelial (RPE) cells expressing different neurotrophic factors. The neutrophic factors were Axokine, brain derived-neurotrophic factor (BDNF), and basic fibroblast growth factor (bFGF). The enhanced green fluorescence protein (eGFP) gene was used as a reporter gene. These genes were transduced into RPE cells by lipofection, selected by antibiotics, and transplanted into the subretinal space of 108 rats. The rats were examined at 1 week and 3 months after the transplantation to determine whether the transduced cells were present, were expressing the protein, and were able to protect photoreceptors against phototoxicity. The survival of the transplanted cells was monitored by the presence of eGFP. The degree of protection was determined by the thickness of the outer nuclear layer. Our results showed that the degree of photoreceptor protection was different for the different types of neurotrophic factors at 1 week. After 3 months, the number of surviving transplanted cell was markedly reduced, and protection was observed only with the BDNF-transduced RPE cells. A significant degree of rescue was also observed by BDNF-transduced RPE cells in the nontransplanted area of the retina at both the early and late times. Lymphocytic infiltration was not detected in the vitreous, retina, and choroid at any time. We conclude that the transplantation of BDNF-transduced RPE cells can reduce the photoreceptor damage induced by phototoxicity in the transplanted area and weakly in the nontransplanted area.
Abe
Toshiaki
T
Division of Clinical Cell Therapy, School of Medicine, Tohoku University, Sendai, Miyagi, Japan. toshi@oph.med.tohoku.ac.jp
Saigo
Yoko
Y
Hojo
Masayoshi
M
Kano
Tetsuya
T
Wakusawa
Ryosuke
R
Tokita
Yumi
Y
Tamai
Makoto
M
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D002470:Cell Survival; D017690:Cell Transplantation; D020934:Ciliary Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D017484:Dermatitis, Phototoxic / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D008027:Light / Q000009:adverse effects*; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D010857:Pigment Epithelium of Eye / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000502:physiology*; D014161:Transduction, Genetic
D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D009414:Nerve Growth Factors; D016222:Fibroblast Growth Factor 2; D049452:Green Fluorescent Proteins; C118937:axokine