Univocal identification of retinal ganglion cells(RGCs) is an essential prerequisite for studying their degeneration and neuroprotection. Before the advent of phenotypic markers, RGCs were normally identified using re...Univocal identification of retinal ganglion cells(RGCs) is an essential prerequisite for studying their degeneration and neuroprotection. Before the advent of phenotypic markers, RGCs were normally identified using retrograde tracing of retinorecipient areas. This is an invasive technique, and its use is precluded in higher mammals such as monkeys. In the past decade, several RGC markers have been described. Here, we reviewed and analyzed the specificity of nine markers used to identify all or most RGCs, i.e., pan-RGC markers, in rats, mice, and macaques. The best markers in the three species in terms of specificity, proportion of RGCs labeled, and indicators of viability were BRN3A, expressed by vision-forming RGCs, and RBPMS, expressed by vision-and non-vision-forming RGCs. NEUN, often used to identify RGCs, was expressed by non-RGCs in the ganglion cell layer, and therefore was not RGC-specific. γ-SYN, TUJ1, and NF-L labeled the RGC axons, which impaired the detection of their somas in the central retina but would be good for studying RGC morphology. In rats, TUJ1 and NF-L were also expressed by non-RGCs. BM88, ERRβ,and PGP9.5 are rarely used as markers, but they identified most RGCs in the rats and macaques and ERRβ in mice. However, PGP9.5 was also expressed by non-RGCs in rats and macaques and BM88 and ERRβ were not suitable markers of viability.展开更多
利用调节型共源共栅电路结构(RGC)可以使跨阻放大器得到较高的带宽,并且通过级联并联-并联负反馈电路可以使增益得到提高。采用0.5μm的标准互补型金属氧化物半导体(CMOS)工艺进行设计,仿真。测试结果表明,该电路具有69.93 d B的跨阻增...利用调节型共源共栅电路结构(RGC)可以使跨阻放大器得到较高的带宽,并且通过级联并联-并联负反馈电路可以使增益得到提高。采用0.5μm的标准互补型金属氧化物半导体(CMOS)工艺进行设计,仿真。测试结果表明,该电路具有69.93 d B的跨阻增益,830 MHz的-3 dB带宽。在输入电流为1μA时,其输出电压的动态摆幅达到4.5 mV,在5 V电源电压下功耗仅为63.16 mW。展开更多
Slit-Robo GTPase-activating protein 2(SRGAP2) plays important roles in axon guidance, neuronal migration, synapse formation, and nerve regeneration. However, the role of SRGAP2 in neuroretinal degenerative disease rem...Slit-Robo GTPase-activating protein 2(SRGAP2) plays important roles in axon guidance, neuronal migration, synapse formation, and nerve regeneration. However, the role of SRGAP2 in neuroretinal degenerative disease remains unclear. In this study, we found that SRGAP2 protein was first expressed in the retina of normal mice at the embryonic stage and was mainly located in the mature retinal ganglion cell layer and the inner nuclear layer. SRGAP2 protein in the retina and optic nerve increased after optic nerve crush. Then, we established a heterozygous knockout(Srgap2+/–) mouse model of optic nerve crush and found that Srgap2 suppression increased retinal ganglion cell survival, lowered intraocular pressure, inhibited glial cell activation, and partially restored retinal function. In vitro experiments showed that Srgap2 suppression activated the mammalian target of rapamycin signaling pathway. RNA sequencing results showed that the expression of small heat shock protein genes(Cryaa, Cryba4, and Crygs) related to optic nerve injury were upregulated in the retina of Srgap2+/– mice. These results suggest that Srgap2 suppression reduced the robust activation of glial cells, activated the mammalian target of rapamycin signaling pathway related to nerve protein, increased the expression of small heat shock protein genes, inhibited the degeneration of retinal ganglion cells, and partially restored optic nerve function.展开更多
A 3.125-Gb/s transimpedance amplifier（TIA） for an optical communication system is realized in 0.35μm CMOS technology.The proposed TIA employs a regulated cascode configuration as the input stage, and adopts DC-canc...A 3.125-Gb/s transimpedance amplifier（TIA） for an optical communication system is realized in 0.35μm CMOS technology.The proposed TIA employs a regulated cascode configuration as the input stage, and adopts DC-cancellation techniques to stabilize the DC operating point.In addition,noise optimization is processed. The on-wafer measurement results show the transimpedance gain of 54.2 dBΩand -3 dB bandwidth of 2.31 GHz.The measured average input referred noise current spectral density is about 18.8 pA/（？）.The measured eye diagram is clear and symmetrical for 2.5-Gb/s and 3.125-Gb/s PRBS.Under a single 3.3-V supply voltage,the TIA consumes only 58.08 mW,including 20 mW from the output buffer.The whole die area is 465×435μm^2.展开更多
基金supported by the Spanish Ministry of Economy and Competitiveness(PID2019-106498GB-I0)Instituto de Salud Carlos III,Fondo Europeo de Desarrollo Regional“Una manera de hacer Europa”(PI19/00071)+2 种基金Fundación Séneca,Agencia de Ciencia y Tecnología Región de Murcia(19881/GERM/15)Spanish Ministry of Science and Innovation(PID 2019-106498 GB-I00)Intramural Research Program of the National Eye Institute,National Institutes of Health(NIH/NEI RO1 EY029087)。
文摘Univocal identification of retinal ganglion cells(RGCs) is an essential prerequisite for studying their degeneration and neuroprotection. Before the advent of phenotypic markers, RGCs were normally identified using retrograde tracing of retinorecipient areas. This is an invasive technique, and its use is precluded in higher mammals such as monkeys. In the past decade, several RGC markers have been described. Here, we reviewed and analyzed the specificity of nine markers used to identify all or most RGCs, i.e., pan-RGC markers, in rats, mice, and macaques. The best markers in the three species in terms of specificity, proportion of RGCs labeled, and indicators of viability were BRN3A, expressed by vision-forming RGCs, and RBPMS, expressed by vision-and non-vision-forming RGCs. NEUN, often used to identify RGCs, was expressed by non-RGCs in the ganglion cell layer, and therefore was not RGC-specific. γ-SYN, TUJ1, and NF-L labeled the RGC axons, which impaired the detection of their somas in the central retina but would be good for studying RGC morphology. In rats, TUJ1 and NF-L were also expressed by non-RGCs. BM88, ERRβ,and PGP9.5 are rarely used as markers, but they identified most RGCs in the rats and macaques and ERRβ in mice. However, PGP9.5 was also expressed by non-RGCs in rats and macaques and BM88 and ERRβ were not suitable markers of viability.
基金supported by the Notional Natural Science Foundation of China,Nos.81770918 (to ZLC),31871383 (to TL)the Natural Science Foundation of Zhejiang Province,No.LY16H120006 (to ZLC)the Departmental Funds from Wenzhou Medical University,No.89214018 (to ZLC)。
文摘Slit-Robo GTPase-activating protein 2(SRGAP2) plays important roles in axon guidance, neuronal migration, synapse formation, and nerve regeneration. However, the role of SRGAP2 in neuroretinal degenerative disease remains unclear. In this study, we found that SRGAP2 protein was first expressed in the retina of normal mice at the embryonic stage and was mainly located in the mature retinal ganglion cell layer and the inner nuclear layer. SRGAP2 protein in the retina and optic nerve increased after optic nerve crush. Then, we established a heterozygous knockout(Srgap2+/–) mouse model of optic nerve crush and found that Srgap2 suppression increased retinal ganglion cell survival, lowered intraocular pressure, inhibited glial cell activation, and partially restored retinal function. In vitro experiments showed that Srgap2 suppression activated the mammalian target of rapamycin signaling pathway. RNA sequencing results showed that the expression of small heat shock protein genes(Cryaa, Cryba4, and Crygs) related to optic nerve injury were upregulated in the retina of Srgap2+/– mice. These results suggest that Srgap2 suppression reduced the robust activation of glial cells, activated the mammalian target of rapamycin signaling pathway related to nerve protein, increased the expression of small heat shock protein genes, inhibited the degeneration of retinal ganglion cells, and partially restored optic nerve function.
基金Project supported by the National High Technology Research and Development Program of China(No.2006AA012284)
文摘A 3.125-Gb/s transimpedance amplifier（TIA） for an optical communication system is realized in 0.35μm CMOS technology.The proposed TIA employs a regulated cascode configuration as the input stage, and adopts DC-cancellation techniques to stabilize the DC operating point.In addition,noise optimization is processed. The on-wafer measurement results show the transimpedance gain of 54.2 dBΩand -3 dB bandwidth of 2.31 GHz.The measured average input referred noise current spectral density is about 18.8 pA/（？）.The measured eye diagram is clear and symmetrical for 2.5-Gb/s and 3.125-Gb/s PRBS.Under a single 3.3-V supply voltage,the TIA consumes only 58.08 mW,including 20 mW from the output buffer.The whole die area is 465×435μm^2.
文摘目的观察大鼠视神经钳夹伤后不同时间的病理学变化及其修复规律。方法成年 S-D 大鼠36只,随机等分为6组:一组为正常对照,其余均用70g 压力的显微无创血管钳于右眼球后1mm 处夹持视神经15s,分别于损伤后3、7、14、30、60 d 取材,观察视神经轴突和视网膜神经节细胞(RGC)的形态及数目变化。结果正常大鼠视神经髓鞘完整,损伤后3 d、7 d,髓鞘疏松解体,轴突内线粒体肿胀,伤后14 d 胶质细胞开始增生,伤后60 d 可见到新生样轴突。正常大鼠 RGC 单层排列,神经纤维层(RNFL)厚度均匀,伤后3 d、7 d,RGC 胞浆中线粒体肿胀明显,尼氏体减少,RNFL 水肿,之后上述改变程度减轻,部分恢复。轴突数目正常为555.00±93.80(单位:个/3258.04 μm^2),视乳头两侧各1mm 的视网膜切片 RGC 数目,正常为69.75±5.38(单位:个),损伤后均逐渐减少,至60 d 时稍增多。结论夹持大鼠视神经70 g 压力15 s 可造成中等程度的损伤,表现在轴突和RGC 的形态异常及数目减少,改变随时间加重,至1个月左右开始恢复。
