Comparative study of histopathology changes between the PS1/APP double transgenic mouse model and Aβ_(1-40)-injected rat model of Alzheimer disease

Objective To identify the genetype of the PS1/APP double transgenic mouse model, then to analyse the histopathological changes in the brain and compare the differences between the transgenic mice models and Aβ_(1-40)-injected rats models of Alzheimer disease. Methods The modified congo red staining, Nissl's staining and immunohistology staining was used to observe the Aβ deposits, activation of astrocyte respectively. Results ①The PS1/APP transgenic mouse extensively displayed Aβ deposits in the cortex and hippocampal structures, and GFAP positive cells were aggregated in mass and surrounded the congo red-positive plaque. ②The Aβ_(1-40)-intrahippocampal-injected rat model showed the Aβ plaque deposits in the dentate gyrus of the hippocampus, with the astrocyte surrounded. The neurons loss was significant in the injection point and pin hole of injection with Nissl's staining methods. GFAP-positive cells increased significantly compared with the uninjected lateral of the hippocampus. Conclusion Although Aβ_(1-40)-injected rat models could simulate some characteristic pathological features of human Alzheimer diseases, Aβ deposits and neurons loss in partial hippocampal, it would not simulate the progressive degenenration in the brain of AD. The double transgenie PS1/APP mice could simulate the specific pathogenesis and progressive changes of AD, mainly is Aβ deposits and the spongiocyte response, while no neurons loss were observed in this model.

Biosafety of a 3D-printed intraocular lens made of a poly (acrylamide-co-sodium acrylate) hydrogel in vitro and in vivo

AIM:To assess the biosafety of a poly(acrylamide-cosodium acrylate)hydrogel(PAH)as a 3D-printed intraocular lens(IOL)material.METHODS:The biosafety of PAH was first evaluated in vitro using human lens epithelial cells(LECs)and the ARPE19 cell line,and a cell counting kit-8(CCK-8)assay was performed to investigate alterations in cell proliferation.A thin film of PAH and a conventional IOL were intraocularly implanted into the eyes of New Zealand white rabbits respectively,and a sham surgery served as control group.The anterior segment photographs,intraocular pressure(IOP),blood parameters and electroretinograms(ERG)were recorded.Inflammatory cytokines in the aqueous humor,such as TNFαand IL-8,were examined by ELISA.Cell apoptosis of the retina was investigated by TUNEL assay,and macro PAHge activation was detected by immunostaining.RESULTS:PAH did not slow cell proliferation when cocultured with human LECs or ARPE19 cells.The implantation of a thin film of a 3 D-printed IOL composed of PAH did not affect the IOP,blood parameters,ERG or optical structure in any of the three experimental groups(n=3 for each).Both TNFαand IL-8 in the aqueous humor of PAH group were transiently elevated 1 wk post-operation and recovered to normal levels at 1 and 3 mo post-operation.Iba1+macroPAHges in the anterior chamber angle in PAH group were increased markedly compared to those of the control group;however,there was no significant difference compared to those in the IOL group.CONCLUSION:PAH is a safe material for 3D printing of personal IOLs that hold great potential for future clinical applications.

Promotion of axon regeneration and inhibition of astrocyte activation by alpha A-crystallin on crushed optic nerve

AIM：To explore the effects of αA-crystallin in astrocyte gliosis after optic nerve crush（ONC） and the mechanism of α-crystallin in neuroprotection and axon regeneration.METHODS：ONC was established on the SpragueDawley rat model and αA-crystallin（10 -4 g/L,4 μL） was intravitreously injected into the rat model.Flash-visual evoked potential（F-VEP） was examined 14 d after ONC,and the glial fibrillary acidic protein（GFAP） levels in the retina and crush site were analyzed 1,3,5,7 and 14 d after ONC by immunohistochemistry（IHC） and Western blot respectively.The levels of beta Tubulin（TUJ1）,growth-associated membrane phosphoprotein-43（GAP-43）,chondroitin sulfate proteoglycans（CSPGs） and neurocan were also determined by IHC 14 d after ONC.RESULTS：GFAP level in the retina and the optic nerve significantly increased 1d after ONC,and reached the peak level 7d post-ONC.Injection of αA-crystallin significantly decreased GFAP level in both the retina and the crush site 3d after ONC,and induced astrocytes architecture remodeling at the crush site.Quantification of retinal ganglion cell（RGC） axons indicated αAcrystallin markedly promoted axon regeneration in ONC rats and enhanced the regenerated axons penetrated into the glial scar.CSPGs and neurocan expression also decreased 14 d after αA-crystallin injection.The amplitude（N1-P1） and latency（P1） of F-VEP were also restored.CONCLUSION：Our results suggest α-crystallin promotes the axon regeneration of RGCs and suppresses the activation of astrocytes.

Perineuronal nets increase inhibitory GABAergic currents during the critical period in rats

AIM: To investigate inhibitory γ-aminobutyric acid (GABA) ergic postsynaptic currents (IPSCs) and postsynaptic currents (PSCs) in layer IV of the rat visual cortex during the critical period and when plasticity was extended through dissolution of the perineuronal nets (PNNs). METHODS: We employed 24 normal Long-Evans rats to study GABA A-PSC characteristics of neurons within layer IV of the visual cortex during development. The animals were divided into six groups of four rats according to ages at recording: PW3 (P21 -23d), PW4 (P28 -30d), PW5 (P35-37d), PW6 (P42-44d), PW7 (P49-51d), and PW8 (56-58d). An additional 24 chondroitin sulfate proteoglycan (CSPG) degradation rats (also Long-Evans) were generated by making a pattern of injections of chondroitinase ABC (chABC) into the visual cortex 1 week prior to recording at PW3, PW4, PW5, PW6, PW7, and PW8. Immunohistochemistry was used to identify the effect of chABC injection on CSPGs. PSCs were detected with whole-cell patch recordings, and GABA A receptor-mediated IPSCs were pharmacologically isolated. RESULTS: IPSC peak current showed a strong rise in the age-matched control group, peaked at PW5 and were maintained at a roughly constant value thereafter. Although there was a small increase in peak current for the chABC group with age, the peak currents continued to decrease with the delayed highest value at PW6, resulting in significantly different week-by-week com-parison with normal development. IPSC decay time continued to increase until PW7 in the control group, while those in the chABC group were maintained at astable level after an initial increase at PW4. Compared with normal rats, the decay times recorded in the chABC rats were always shorter, which differed significantly at each age. We did not observe any differences in IPSC properties between the age-matched control and penicillinase (P-ase) group. However, the change in IPSCs after chABC treatment was not reflected in the total PSCs or in basic membrane properties in layer IV of the rat visual cortex. CONCLUSION: Our results demonstrate that rather than rapidly increasing during the critical period for neuronal plasticity, IPSCs in layer IV of rat visual cortex are maintained at an immature level when PNNs are removed by chABC. This suggests that GABA receptor maturation involves the conformation of the CSPGs in PNNs.

Intravitreally injected ranibizumab versus photodynamic therapy for CNV secondary to choroidal osteoma:a 7-year follow-up case report

Dear Editor,We present a case of bilateral choroidal neovascularization(CNV)secondary to choroidal osteoma involving the macula and investigate the effect of intravitreal injection of ranibizumab and photodynamic therapy(PDT)in a sevenyear follow-up.Informed consent for patient information and images to be published was obtained from the patient included in the study based on the Declaration of Helsinki,which was approved by the Ethics Committee of Southwest Hospital.

含非连续支撑的非对称交叉斜撑体系的计算长度系数（英文）

目的:非矩形平面框架致使其交叉斜撑体系具有非对称性,而采用了非连续支撑的非对称非连续交叉支撑体系的面外稳定问题更为复杂。本文旨在通过建立无量纲稳定特征方程,从理论上深入阐释该交叉支撑体系的面外屈曲特征,并为工程设计提供显式的压杆计算长度系数的计算公式。创新点:1.建立一般情况下非对称非连续交叉斜撑体系的无量纲特征方程;2.针对各种可能受力工况,详细分析该交叉支撑体系的面外屈曲特征,并给出理论解释;3.提出非对称非连续交叉斜撑体系中压杆计算长度系数的显式经验计算公式。方法:1.通过对非对称非连续交叉支撑体系进行弹性面外屈曲建模,以及稳定平衡方程的无量纲化,推导出其相应的特征方程;2.通过变量替换,揭示其内在对称性,从而为经验公式的构造提供依据;3.针对各种受力工况,进行求解域分析和确定,完成特征方程的求解,以进行面外屈曲特征分析,并提出压杆计算长度系数的经验公式;4.利用经验公式对多个实例进行计算,并与基于有限元的刚度法结果以及以往的文献数据进行比较,以验证经验公式的可靠性。结论:1.推导出了非对称非连续交叉斜撑体系的特征方程;采用无量纲参数后,该方程具有一般性。2.通过变量替换,该方程可以转换为与单轴几何对称交叉斜撑相同的特征方程形式。3.当交叉斜撑中的连续杆和非连续杆同时受压时,非连续杆将率先失稳。4.针对各种受力工况,提出了交叉支撑体系的压杆计算长度系数的显式经验公式,且计算结果兼具可靠性和准确性。