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默克密理博官方微博中科院生物物理所何士刚教授
中科院生物物理所何士刚教授
Ruotong Ren1, Ying Li1, Zhiping Liu1, Kegao Liu2 and Shigang He1*
1State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics,
Chinese Academy of Sciences, Beijing, China
2Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, China.
Purpose: To evaluate the long-term rescue of rat retinal ganglion cells (RGCs) and visual functions after acute elevation of intraocular pressure (IOP) by expressing brain-derived neurotrophic factor (BDNF) using adeno-associated viral (AAV) vector.
Methods: AAV vector was constructed to express BDNF and injected into the vitreous 6 hours after transient IOP elevation to 130 mmHg. The rescue effects were evaluated by 1) counting RGCs retrogradely labeled with fluorogold (FG) injected into the superior colicullus, 2) measuring amplitude and latency of the P1 component of the visual evoked potential (VEP) and 3) behavioral tests for visual acuity and contrast sensitivity.
Results: RGCs underwent continuous decrease up to 9 weeks after insult. The number of FG-positive RGCs was significantly increased in the retinas treated with AAV-mediated BDNF expression 3, 6 and 9 weeks after insult with corresponding improvements in the amplitude and latency of the VEP. Supplementing recombinant BDNF protein once to compensate for the slow onset of AAV-mediated gene expression achieved much greater rescue both in the number of RGCs and the VEP parameters. In behavioral tests, visual acuity and contrast sensitivity were significantly increased in all treated groups, largest in the combined therapy group. The improvements in visual acuity and contrast sensitivity were maintained for 52 weeks without causing any apparent discomfort. We further demonstrated that BDNF rescued RGCs through activating TrkB receptors through both autocrine and paracrine mechanisms.
编辑: cq
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