Intraocular gene transfer of ciliary neurotrophic factor rescues photoreceptor degeneration in RCS rats.
Ciliary neurotrophic factor (CNTF) is known as an important factor in the regulation of retinal cell growth. We used both recombinant CNTF and an adenovirus carrying the CNTF gene to regulate retinal photoreceptor expression in a retinal degenerative animal, Royal College of Surgeons (RCS) rats. Cells in the outer nuclear layer of the retinae from recombinant-CNTF-treated, adenoviral-CNTF-treated, saline-operated, and contralateral untreated preparations were examined for those exhibiting CNTF photoreceptor protective effects. Cell apoptosis in the outer nuclear layer of the retinae was also detected. It was found that CNTF had a potent effect on delaying the photoreceptor degeneration process in RCS rats. Furthermore, adenovirus CNTF gene transfer was proven to be better at rescuing photoreceptors than that when using recombinant CNTF, since adenoviral CNTF prolonged the photoreceptor protection effect. The function of the photoreceptors was also examined by taking electroretinograms of different animals. Adenoviral-CNTF-treated eyes showed better retinal function than did the contralateral control eyes. This study indicates that adenoviral CNTF effectively rescues degenerating photoreceptors in RCS rats.
Huang
Shun-Ping
SP
Department of Ophthalmology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
Lin
Po-Kang
PK
Liu
Jorn-Hon
JH
Khor
Chin-Ni
CN
Lee
Yih-Jing
YJ
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D020934:Ciliary Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D004596:Electroretinography; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D020287:In Situ Nick-End Labeling; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000473:pathology*; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
D020934:Ciliary Neurotrophic Factor