高级检索
中华实验眼科杂志
期刊首页
过刊列表
高级检索
稿件发表
• 实验研究 •
ENGLISH ABSTRACT
新型纳米睫状神经营养因子复合物玻璃体腔注射对食蟹猴眼部的安全性——形态学评价
张天璐
刘一帆
沈吟
作者及单位信息
·
DOI： 10.3760/cma.j.cn115989-20220212-00052
Ocular safety of intravitreal injection of a novel nanoparticle ciliary neurotrophic factor complex in cynomolgus macaques——a morphological evaluation
Zhang Tianlu
Liu Yifan
Shen Yin
Authors Info & Affiliations
Zhang Tianlu
Eye Center, Renmin Hospital of Wuhan University, Wuhan 430060, China
Liu Yifan
Eye Center, Renmin Hospital of Wuhan University, Wuhan 430060, China
Shen Yin
Eye Center, Renmin Hospital of Wuhan University, Wuhan 430060, China
Medical Research Institute, Wuhan University, Wuhan 430071, China
·
DOI： 10.3760/cma.j.cn115989-20220212-00052
205
46
0
0
0
0
PDF下载
APP内阅读
摘要

目的评估一种新型纳米神经营养因子复合物(NP-CNTFs)在非人灵长类动物眼内应用的安全性。

方法利用纳米工艺制备包裹睫状神经营养因子(CNTF)的纳米粒。选取3只成年雄性食蟹猴，单眼玻璃体腔注射10 μl NP-CNTFs(1 μg/μl)作为NP-CNTFs组，对侧眼注射等体积磷酸盐缓冲液作为对照组。在注射前、注射后第3天和第7天，对食蟹猴行常规眼前节检查以评估结膜充血、前房闪辉及前房细胞等眼部症状并评分；采用彩色眼底照相观察眼底情况；采用频域光学相干断层扫描(SD-OCT)检测视网膜形态结构及厚度。

结果所制备NP-CNTFs粒径为(317±3)nm，多分散性指数为0.042±0.015，Zeta电位为(－38.9±0.7)mV，具备较好的稳定性、生物利用度和生物相容性。眼前节检查显示，NP-CNTFs组在注射后第3天表现出较对照组稍明显的结膜充血、前房闪辉和前房细胞，但在注射后第7天基本恢复正常。NP-CNTFs组与对照组注射后第3天眼前节症状评分分别为(2.67±0.88)和(1.00±0.58)分，注射后第7天分别为(0.67±0.33)和(0.33±0.33)分，组间比较差异均无统计学意义( t＝2.50、1.00，均 P>0.05)。彩色眼底照相结果显示，NP-CNTFs组和对照组在注射后第7天眼底均正常，未见玻璃体混浊、玻璃体出血、视网膜出血或视盘水肿等异常改变。SD-OCT结果显示，NP-CNTFs组和对照组在注射后第7天均未见明显视网膜组织学改变。NP-CNTFs组和对照组视网膜神经纤维层厚度分别为(107.67±0.88)和(111.00±3.22)μm，黄斑中央凹厚度分别为(255.67±2.03)和(254.67±3.84)μm，组间比较差异均无统计学意义( t＝1.43、0.50，均 P>0.05)。

结论新型纳米药物NP-CTNFs在食蟹猴眼内应用的安全性较好。

纳米粒;睫状神经营养因子;食蟹猴;安全性评估
ABSTRACT

ObjectiveTo evaluate the safety of a novel nanoparticle neurotrophic factor complex for intraocular application in non-human primates.

MethodsNanoparticles incorporated with ciliary neurotrophic factor (NP-CNTFs) were produced utilizing nanotechnology.Three adult male cynomolgus macaques were included and intravitreally injected with 10 μl NP-CNTFs at a concentration of 1 μg/μl into one of the two eyes, and these three eyes were designated as the NP-CNTFs group.The contralateral eyes received the same volume of phosphate buffered saline and were designated as the control group.Before the injection and on days 3 and 7 after the injection, routine clinical examinations of the anterior segment were performed to evaluate the ocular clinical symptoms such as conjunctival congestion, anterior chamber flare and cells.The fundus condition was observed by fundus photography.The morphological structure and thickness of retinas were detected by spectral domain-optical coherence tomography (SD-OCT).The use and care of animals were in accordance with the Guide for the Care and Use of Laboratory Animals issued by the National Institutes of Health and the standards of Association for Assessment and Accreditation of Laboratory Animal Care.The study protocol complied with the ethics of laboratory animal welfare and was approved by Hubei Topgene Biotechnology Co., Ltd.(No.IACUC-2019-012).

ResultsThe NP-CNTFs prepared in this study had a particle size of (317±3)nm, a polydispersity index of 0.042±0.015, and a zeta potential of (-38.9±0.7)mV, and exhibited relatively good stability, bioavailability, and biocompatibility.Clinical examinations revealed that the clinical manifestations of conjunctival congestion, anterior chamber flare and cells were slightly more obvious in the NP-CNTFs group at 3 days after injection compared to the control group, but basically returned to normal at 7 days after injection.The scores of anterior-segment clinical symptoms of the NP-CNTFs and control group were (2.67±0.88) and (1.00±0.58) at 3 days after injection, and (0.67±0.33) and (0.33±0.33) at 7 days after injection, respectively, with no statistical differences between them ( t=2.50, 1.00; both at P>0.05).Fundus photography showed normal fundus in both groups at 7 days after injection with no abnormal changes including vitreous opacity, vitreous hemorrhage, retinal hemorrhage or papilloedema.SD-OCT showed no significant histological changes in the retinas at 7 days after injection in both groups.The retinal nerve fiber layer thickness of the NP-CNTFs and control group were (107.67±0.88) and (111.00±3.22)μm, respectively, and the macular foveal thickness of the two groups were (255.67±2.03) and (254.67±3.84)μm, respectively, with no statistical differences between them ( t=1.43, 0.50; both at P>0.05).

ConclusionsThe complex NP-CNTFs shows good safety for intraocular application in cynomolgus macaques.

Nanoparticles;Ciliary neurotrophic factor;Cynomolgus macaques;Safety evaluation
Shen Yin, Email: nc.defudabe.uhwnehsniy
Copyright by Chinese Medical Association
No content published by the journals of Chinese Medical Association may be reproduced or abridged without authorization. Please do not use or copy the layout and design of the journals without permission.
All articles published represent the opinions of the authors, and do not reflect the official policy of the Chinese Medical Association or the Editorial Board, unless this is clearly specified.
引用本文

张天璐,刘一帆,沈吟. 新型纳米睫状神经营养因子复合物玻璃体腔注射对食蟹猴眼部的安全性——形态学评价[J]. 中华实验眼科杂志,2024,42(07)：613-620.

DOI:10.3760/cma.j.cn115989-20220212-00052

PERMISSIONS

Request permissions for this article from CCC.

评价本文
*以上评分为匿名评价

版权归中华医学会所有。

未经授权，不得转载、摘编本刊文章，不得使用本刊的版式设计。

除非特别声明，本刊刊出的所有文章不代表中华医学会和本刊编委会的观点。

视网膜退行性疾病是全世界致盲的主要原因之一，目前临床上尚无有效的预防和治疗方法 [ 1 , 2 , 3 ]。睫状神经营养因子(ciliary neurotrophic factor，CNTF)、脑源性神经营养因子、胶质细胞源性神经营养因子等在以视网膜神经节细胞损伤为主要表现的神经退行性疾病及遗传性视网膜退行性疾病中均表现出一定的神经保护作用，其中对于CNTF的研究尤为广泛 [ 4 , 5 , 6 , 7 ]。研究表明，CNTF可在视网膜变性过程中延缓光感受器细胞死亡，并促进视锥细胞外节再生；此外，其还通过影响视网膜色素上皮细胞的生理特性以及其他细胞因子/神经营养因子的分泌调节远端视网膜/视网膜色素上皮/Bruch膜复合体微环境，对视网膜组织表现出一定的保护作用 [ 7 , 8 , 9 ]。据报道，CNTF可降低视网膜退行性疾病动物模型中光感受器细胞死亡导致的视力丧失的发生率 [ 10 , 11 ]。然而，CNTF半衰期较短，治疗过程中需进行多次玻璃体腔注射以维持长期疗效，而多次注射引起眼内炎、视网膜脱离、视网膜血管阻塞等一系列严重并发症的发生风险增加 [ 12 , 13 ]。因此，寻求安全、长效的CNTF治疗方法至关重要。纳米粒作为一种新型药物递送载体，可实现缓释、控释和靶向给药，从多方面提高了药物治疗的安全性、有效性和可靠性。在众多纳米粒载体中，硫酸葡聚糖－壳聚糖纳米载体(dextran sulfate-chitosan nanoparticles，DSCS NPs)尤其适用于蛋白质类药物的递送 [ 14 ]。DSCS NPs可有效包裹并稳定治疗性多肽/蛋白质，提高药物生物利用度，增强治疗效果 [ 15 , 16 , 17 , 18 ]。将CNTF蛋白包裹于DSCS NPs中所制备的一种新型纳米睫状神经营养因子复合物(nanoparticles incorporated with ciliary neurotrophic factor，NP-CNTFs)可通过控制聚合物的性质和降解时间来调控药物的扩散，有望实现单次玻璃体腔注射即达到长效治疗效果。目前，NP-CNTFs玻璃体腔注射的眼部安全性尚不明确。本研究拟制备NP-CNTFs并观察其玻璃体腔注射后对食蟹猴眼部组织的短期影响，探索其应用于非人灵长类动物的眼部安全性，为开发基于纳米粒治疗视网膜退行性疾病的潜在药物提供实验基础。
试读结束，您可以通过登录机构账户或个人账户后获取全文阅读权限。
参考文献
[1]
Bressler NM . Age-related macular degeneration is the leading cause of blindness[J]. JAMA， 2004，291(15)∶1900－1901. DOI： 10.1001/jama.291.15.1900 .
返回引文位置Google Scholar
百度学术
万方数据
[2]
Hartong DT ， Berson EL ， Dryja TP . Retinitis pigmentosa[J]. Lancet， 2006，368(9549)∶1795－1809. DOI： 10.1016/S0140-6736(06)69740-7 .
返回引文位置Google Scholar
百度学术
万方数据
[3]
Mitchell P ， Liew G ， Gopinath B ，et al. Age-related macular degeneration[J]. Lancet， 2018，392(10153)∶1147－1159. DOI： 10.1016/S0140-6736(18)31550-2 .
返回引文位置Google Scholar
百度学术
万方数据
[4]
Wenzel A ， Grimm C ， Samardzija M ，et al. Molecular mechanisms of light-induced photoreceptor apoptosis and neuroprotection for retinal degeneration[J]. Prog Retin Eye Res， 2005，24(2)∶275－306. DOI： 10.1016/j.preteyeres.2004.08.002 .
返回引文位置Google Scholar
百度学术
万方数据
[5]
Fudalej E ， Justyniarska M ， Kasarełło K ，et al. Neuroprotective factors of the retina and their role in promoting survival of retinal ganglion cells：a review[J]. Ophthalmic Res， 2021，64(3)∶345－355. DOI： 10.1159/000514441 .
返回引文位置Google Scholar
百度学术
万方数据
[6]
Faktorovich EG ， Steinberg RH ， Yasumura D ，et al. Photoreceptor degeneration in inherited retinal dystrophy delayed by basic fibroblast growth factor[J]. Nature， 1990，347(6288)∶83－86. DOI： 10.1038/347083a0 .
返回引文位置Google Scholar
百度学术
万方数据
[7]
Wen R ， Tao W ， Li Y ，et al. CNTF and retina[J]. Prog Retin Eye Res， 2012，31(2)∶136－151. DOI： 10.1016/j.preteyeres.2011.11.005 .
返回引文位置Google Scholar
百度学术
万方数据
[8]
Chucair-Elliott AJ ， Elliott MH ， Wang J ，et al. Leukemia inhibitory factor coordinates the down-regulation of the visual cycle in the retina and retinal-pigmented epithelium[J/OL]. J Biol Chem， 2012，287(29)∶24092－24102[2023－10－10]. http://www.ncbi.nlm.nih.gov/pubmed/22645143. DOI： 10.1074/jbc.M112.378240 .
返回引文位置Google Scholar
百度学术
万方数据
[9]
Li R ， Wen R ， Banzon T ，et al. CNTF mediates neurotrophic factor secretion and fluid absorption in human retinal pigment epithelium[J/OL]. PLoS One， 2011，6(9)∶e23148[2023－10－10]. http://www.ncbi.nlm.nih.gov/pubmed/21912637. DOI： 10.1371/journal.pone.0023148 .
返回引文位置Google Scholar
百度学术
万方数据
[10]
LaVail MM ， Yasumura D ， Matthes MT ，et al. Protection of mouse photoreceptors by survival factors in retinal degenerations[J]. Invest Ophthalmol Vis Sci， 1998，39(3)∶592－602.
返回引文位置Google Scholar
百度学术
万方数据
[11]
Liang FQ ， Dejneka NS ， Cohen DR ，et al. AAV-mediated delivery of ciliary neurotrophic factor prolongs photoreceptor survival in the rhodopsin knockout mouse[J]. Mol Ther， 2001，3(2)∶241－248. DOI： 10.1006/mthe.2000.0252 .
返回引文位置Google Scholar
百度学术
万方数据
[12]
Emerich DF ， Thanos CG . Intracompartmental delivery of CNTF as therapy for Huntington's disease and retinitis pigmentosa[J]. Curr Gene Ther， 2006，6(1)∶147－159. DOI： 10.2174/156652306775515547 .
返回引文位置Google Scholar
百度学术
万方数据
[13]
Jonas JB ， Spandau UH ， Rensch F ，et al. Infectious and noninfectious endophthalmitis after intravitreal bevacizumab[J]. J Ocul Pharmacol Ther， 2007，23(3)∶240－242. DOI： 10.1089/jop.2006.0146 .
返回引文位置Google Scholar
百度学术
万方数据
[14]
Wen R ， Song Y ， Kjellstrom S ，et al. Regulation of rod phototransduction machinery by ciliary neurotrophic factor[J/OL]. J Neurosci， 2006，26(52)∶13523－13530[2023－10－10]. http://www.ncbi.nlm.nih.gov/pubmed/17192435. DOI： 10.1523/JNEUROSCI.4021-06.2006 .
返回引文位置Google Scholar
百度学术
万方数据
[15]
Gribova V ， Crouzier T ， Picart C ．A material's point of view on recent developments of polymeric biomaterials：control of mechanical and biochemical properties[J/OL]. J Mater Chem， 2011，21(38)∶14354－14366[2023－10－10]. http://www.ncbi.nlm.nih.gov/pubmed/25067892. DOI： 10.1039/C1JM11372K .
返回引文位置Google Scholar
百度学术
万方数据
[16]
Sullad AG ， Manjeshwar LS ， Aminabhavi TM . Novel semi-interpenetrating microspheres of dextran-grafted-acrylamide and poly (vinyl alcohol) for controlled release of abacavir sulfate[J/OL]. Ind Eng Chem Res， 2011，50(21)∶11778－11784[2023－10－10]. https://pubs.acs.org/doi/10.1021/ie2006438. DOI： 10.1021/ie2006438 .
返回引文位置Google Scholar
百度学术
万方数据
[17]
Lauten EH ， VerBerkmoes J ， Choi J ，et al. Nanoglycan complex formulation extends VEGF retention time in the lung[J]. Biomacromolecules， 2010，11(7)∶1863－1872. DOI： 10.1021/bm100384z .
返回引文位置Google Scholar
百度学术
万方数据
[18]
Yin T ， Bader AR ， Hou TK ，et al. SDF-1α in glycan nanoparticles exhibits full activity and reduces pulmonary hypertension in rats[J]. Biomacromolecules， 2013，14(11)∶4009－4020. DOI： 10.1021/bm401122q .
返回引文位置Google Scholar
百度学术
万方数据
[19]
Zaman P ， Wang J ， Blau A ，et al. Incorporation of heparin-binding proteins into preformed dextran sulfate-chitosan nanoparticles[J]. Int J Nanomedicine， 2016，11∶6149－6159. DOI： 10.2147/IJN.S119174 .
返回引文位置Google Scholar
百度学术
万方数据
[20]
Adler R . Ciliary neurotrophic factor as an injury factor[J]. Curr Opin Neurobiol， 1993，3(5)∶785－789. DOI： 10.1016/0959-4388(93)90154-q .
返回引文位置Google Scholar
百度学术
万方数据
[21]
Chong NH ， Alexander RA ， Waters L ，et al. Repeated injections of a ciliary neurotrophic factor analogue leading to long-term photoreceptor survival in hereditary retinal degeneration[J]. Invest Ophthalmol Vis Sci， 1999，40(6)∶1298－1305.
返回引文位置Google Scholar
百度学术
万方数据
[22]
Cayouette M ， Gravel C ．Adenovirus-mediated gene transfer of ciliary neurotrophic factor can prevent photoreceptor degeneration in the retinal degeneration (rd) mouse[J]. Hum Gene Ther， 1997，8(4)∶423－430. DOI： 10.1089/hum.1997.8.4-423 .
返回引文位置Google Scholar
百度学术
万方数据
[23]
Cayouette M ， Behn D ， Sendtner M ，et al. Intraocular gene transfer of ciliary neurotrophic factor prevents death and increases responsiveness of rod photoreceptors in the retinal degeneration slow mouse[J]. J Neurosci， 1998，18(22)∶9282－9293. DOI： 10.1523/JNEUROSCI.18-22-09282.1998 .
返回引文位置Google Scholar
百度学术
万方数据
[24]
Liang FQ ， Aleman TS ， Dejneka NS ，et al. Long-term protection of retinal structure but not function using RAAV.CNTF in animal models of retinitis pigmentosa[J]. Mol Ther， 2001，4(5)∶461－472. DOI： 10.1006/mthe.2001.0473 .
返回引文位置Google Scholar
百度学术
万方数据
[25]
Bok D ， Yasumura D ， Matthes MT ，et al. Effects of adeno-associated virus-vectored ciliary neurotrophic factor on retinal structure and function in mice with a P216L rds/peripherin mutation[J]. Exp Eye Res， 2002，74(6)∶719－735. DOI： 10.1006/exer.2002.1176 .
返回引文位置Google Scholar
百度学术
万方数据
[26]
Schlichtenbrede FC ， MacNeil A ， Bainbridge JW ，et al. Intraocular gene delivery of ciliary neurotrophic factor results in significant loss of retinal function in normal mice and in the Prph2Rd2/Rd2 model of retinal degeneration[J]. Gene Ther， 2003，10(6)∶523－527. DOI： 10.1038/sj.gt.3301929 .
返回引文位置Google Scholar
百度学术
万方数据
[27]
Hellström M ， Pollett MA ， Harvey AR . Post-injury delivery of rAAV2-CNTF combined with short-term pharmacotherapy is neuroprotective and promotes extensive axonal regeneration after optic nerve trauma[J]. J Neurotrauma， 2011，28(12)∶2475－2483. DOI： 10.1089/neu.2011.1928 .
返回引文位置Google Scholar
百度学术
万方数据
[28]
Birch DG ， Weleber RG ， Duncan JL ，et al. Randomized trial of ciliary neurotrophic factor delivered by encapsulated cell intraocular implants for retinitis pigmentosa[J]. Am J Ophthalmol， 2013，156(2)∶283－292. DOI： 10.1016/j.ajo.2013.03.021 .
返回引文位置Google Scholar
百度学术
万方数据
[29]
Talcott KE ， Ratnam K ， Sundquist SM ，et al. Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic factor treatment[J]. Invest Ophthalmol Vis Sci， 2011，52(5)∶2219－2226. DOI： 10.1167/iovs.10-6479 .
返回引文位置Google Scholar
百度学术
万方数据
[30]
Zhang K ， Hopkins JJ ， Heier JS ，et al. Ciliary neurotrophic factor delivered by encapsulated cell intraocular implants for treatment of geographic atrophy in age-related macular degeneration[J]. Proc Natl Acad Sci U S A， 2011，108(15)∶6241－6245. DOI： 10.1073/pnas.1018987108 .
返回引文位置Google Scholar
百度学术
万方数据
[31]
Birch DG ， Bennett LD ， Duncan JL ，et al. Long-term follow-up of patients with retinitis pigmentosa receiving intraocular ciliary neurotrophic factor implants[J]. Am J Ophthalmol， 2016，170∶10－14. DOI： 10.1016/j.ajo.2016.07.013 .
返回引文位置Google Scholar
百度学术
万方数据
[32]
Hurbankova M ， Volkovova K ， Hraskova D ，et al. Respiratory toxicity of Fe 3 O 4 na noparticles：experimental study [J]. Rev Environ Health， 2017，32(1－2)∶207－210. DOI： 10.1515/reveh-2016-0022 .
返回引文位置Google Scholar
百度学术
万方数据
[33]
Mirshafiee V ， Sun B ， Chang CH ，et al. Toxicological profiling of metal oxide nanoparticles in liver context reveals pyroptosis in kupffer cells and macrophages versus apoptosis in hepatocytes[J]. ACS Nano， 2018，12(4)∶3836－3852. DOI： 10.1021/acsnano.8b01086 .
返回引文位置Google Scholar
百度学术
万方数据
[34]
Yin L ， Ding J ， He C ，et al. Drug permeability and mucoadhesion properties of thiolated trimethyl chitosan nanoparticles in oral insulin delivery[J]. Biomaterials， 2009，30(29)∶5691－5700. DOI： 10.1016/j.biomaterials.2009.06.055 .
返回引文位置Google Scholar
百度学术
万方数据
[35]
Wang X ， Chi N ， Tang X ．Preparation of estradiol chitosan nanoparticles for improving nasal absorption and brain targeting[J]. Eur J Pharm Biopharm， 2008，70(3)∶735－740. DOI： 10.1016/j.ejpb.2008.07.005 .
返回引文位置Google Scholar
百度学术
万方数据
[36]
Huo M ， Zhang Y ， Zhou J ，et al. Synthesis and characterization of low-toxic amphiphilic chitosan derivatives and their application as micelle carrier for antitumor drug[J]. Int J Pharm， 2010，394(1－2)∶162－173. DOI： 10.1016/j.ijpharm.2010.05.001 .
返回引文位置Google Scholar
百度学术
万方数据
[37]
de Campos AM ， Diebold Y ， Carvalho EL ，et al. Chitosan nanoparticles as new ocular drug delivery systems： in vitro stability， in vivo fate，and cellular toxicity [J]. Pharm Res， 2004，21(5)∶803－810. DOI： 10.1023/b:pham.0000026432.75781.cb .
返回引文位置Google Scholar
百度学术
万方数据
[38]
Agnihotri SA ， Mallikarjuna NN ， Aminabhavi TM . Recent advances on chitosan-based micro- and nanoparticles in drug delivery[J]. J Control Release， 2004，100(1)∶5－28. DOI： 10.1016/j.jconrel.2004.08.010 .
返回引文位置Google Scholar
百度学术
万方数据
[39]
Kean T ， Thanou M ．Biodegradation，biodistribution and toxicity of chitosan[J]. Adv Drug Deliv Rev， 2010，62(1)∶3－11. DOI： 10.1016/j.addr.2009.09.004 .
返回引文位置Google Scholar
百度学术
万方数据
[40]
Wang JJ ， Zeng ZW ， Xiao RZ ，et al. Recent advances of chitosan nanoparticles as drug carriers[J]. Int J Nanomedicine， 2011，6∶765－774. DOI： 10.2147/IJN.S17296 .
返回引文位置Google Scholar
百度学术
万方数据
[41]
Zhang J ， Zhan P ， Tian H ．Recent updates in the polysaccharides-based Nano-biocarriers for drugs delivery and its application in diseases treatment：a review[J]. Int J Biol Macromol， 2021，182∶115－128. DOI： 10.1016/j.ijbiomac.2021.04.009 .
返回引文位置Google Scholar
百度学术
万方数据
[42]
Tillgren V ， Onnerfjord P ， Haglund L ，et al. The tyrosine sulfate-rich domains of the LRR proteins fibromodulin and osteoadherin bind motifs of basic clusters in a variety of heparin-binding proteins，including bioactive factors[J/OL]. J Biol Chem， 2009，284(42)∶28543－28553[2023－10－16]. http://www.ncbi.nlm.nih.gov/pubmed/19700767. DOI： 10.1074/jbc.M109.047076 .
返回引文位置Google Scholar
百度学术
万方数据
[43]
Watters DJ ， Hendry IA . Purification of a ciliary neurotrophic factor from bovine heart[J]. J Neurochem， 1987，49(3)∶705－713. DOI： 10.1111/j.1471-4159.1987.tb00951.x .
返回引文位置Google Scholar
百度学术
万方数据
[44]
Yang JY ， Lu B ， Feng Q ，et al. Retinal protection by sustained nanoparticle delivery of oncostatin m and ciliary neurotrophic factor into rodent models of retinal degeneration[J/OL]. Transl Vis Sci Technol， 2021，10(9)∶6[2023－10－26]. http://www.ncbi.nlm.nih.gov/pubmed/34347033. DOI： 10.1167/tvst.10.9.6 .
返回引文位置Google Scholar
百度学术
万方数据
备注信息
A
沈吟，Email： nc.defudabe.uhwnehsniy
B

张天璐：实验设计、研究实施、数据采集、数据统计分析及文章撰写；刘一帆：研究实施及数据采集；沈吟：实验设计、文章审阅及定稿

C
所有作者均声明不存在利益冲突
D
感谢美国生物科技公司Hebecell在纳米药物制备方面提供的支持
E
政府间国际科技创新合作重点专项 (2017YFE0103400)
评论 （0条）
注册
登录
时间排序
暂无评论，发表第一条评论抢沙发
MedAI助手（体验版）
文档即答
智问智答
机器翻译
回答内容由人工智能生成，我社无法保证其准确性和完整性，该生成内容不代表我们的态度或观点，仅供参考。
生成快照
文献快照

你好，我可以帮助您更好的了解本文，请向我提问您关注的问题。

0/2000

《中华医学会杂志社用户协议》 | 《隐私政策》

《SparkDesk 用户协议》 | 《SparkDesk 隐私政策》

网信算备340104764864601230055号 | 网信算备340104726288401230013号

技术支持：

历史对话
本文全部
还没有聊天记录
设置
模式
纯净模式沉浸模式
字号
小中大