ミキ　カツアキ   MIKI KATSUAKI   三木　克朗    所属   関西医科大学  眼科学講座    職種   診療講師
言語種別	英語
発表タイトル	Transgenic Expression of Glial Cell Line-Derived Neurotrophic Factor in Photoreceptors or RPE Delays but Does Not Prevent Photoreceptor Cell Death in rd10 Mice.
会議名	Association for Research in Vision and Ophthalmology 2012 Annual Meeting
学会区分	国際学会及び海外の学会
発表者・共同発表者	◎Ohnaka M,Miki K, Yuan-Yuan Gong, Rebecca Stevens, Iwase T, Sean F. Hackett, Peter A. Campochiaro
発表年月日	2012/05
開催地 （都市, 国名）	Fort Lauderdale, FL, USA
概要	Purpose: Glial cell line-derived neurotrophic factor (GDNF) is a secreted factor that has been shown to promote survival of photoreceptors. We tested the effect of high expression of GDNF in photoreceptors or RPE in rd10 mice. Methods: Mice that carry the rd10 mutation and have doxycycline (Dox)-inducible expression of GDNF in photoreceptors, IRBP/rtTA-TRE/GDNF-rd10 (IRBP/GDNF/rd10), or RPE, VMD2/rtTA-TRE/GDNF-rd10 (VMD2/GDNF/rd10) were generated. The level of Gdnf mRNA in the eye was measured at P35, P50, and P70. Rod photoreceptor survival was assessed by measuring outer nuclear layer (ONL) thickness, cone photoreceptor survival was assessed by measuring cone density on peanut agglutinin stained retinal whole mounts, and retinal function was assessed by electroretinograms (ERGs). Results: The level of Gdnf mRNA was 200-fold higher in eyes of Dox-treated IRBP/GDNF/rd10 mice compared to Dox-treated VMD2/GDNF/rd10 mice at P35 and although there was a significant drop at P50 and P70, levels were still more than 10-fold higher in IRBP/GDNF/rd10 mice. Despite the lower GDNF expression, VMD2/GDNF/rd10 mice had significantly thicker ONL than rd10 mice at 6/6 measurement locations, while IRBP/GDNF/rd10 mice had thicker ONL than rd10 mice at 3/6 locations. Compared to rd10 mice, VMD2/GDNF/rd10 and IRBP/GDNF/rd10 mice had significantly greater mean scotopic and photopic b-wave amplitudes at P35, P50, P60, and P70 and not different from each other, except mean photopic b-wave at P35 which was greater for VMD2/GDNF/rd10 mice compared to IRBP/GDNF/rd10 mice. Cone density was significantly greater in VMD2/GDNF/rd10 and IRBP/GDNF/rd10 mice compared to rd10 mice at P50, but by P70 it had decreased substantially in both. Conclusions: High expression of GDNF in RPE cells or very high expression of GDNF in photoreceptors of rd10 mice promoted temporary survival of rods and cones and preservation of their ERG function.