兔眼玻璃体腔注射抗血管内皮生长因子单克隆抗体Bevacizumab的视网膜毒性研究

目的 观察不同剂量抗血管内皮生长因子单克隆抗体Bevacizumab兔眼玻璃体腔注射的视网膜毒性作用。 方法 16只新西兰无色素兔的32只眼随机分为药物注射组和对照组，药物注射组又根据玻璃体腔注射药物剂量不同分为A、B、C组，玻璃体腔注射Bevacizumab剂量分别为0.05、0.10、0.25 ml，分别含Bevacizumab 1.25、2.50、6.25 mg。对照组玻璃体腔注射0.9％生理盐水0.10 ml。注药后1、2、4周行视网膜电图（ERG）检查。另外 ，在兔眼玻璃体腔注射Bevacizumab后1、2、4周，每组各摘除2只兔眼，行视网膜组织形态及超 微结构的光学显微镜和透射电子显微镜观察。 结果 兔眼玻璃体腔注射 Bevacizumab后1、2、4周，兔眼ERG各项反应波形均正常，振幅均未出现异常改变（P＞0.05）。光学显微镜下观察 ，药物注射组和对照组视网膜各层组织形态在各时间点均未见异常。透射电子显微镜观察， A、B组与对照组无明显差异；C组视网膜光感受器细胞出现部分线粒体损伤，发生肿胀和积 水变，4周时病变无缓解。 结论 单次兔眼玻璃体腔注射Bevacizumab 1.25 mg或2.50 mg是安全的。 （中华眼底病杂志，2008，24：193-196）     

兔眼玻璃体腔注射抗血管内皮生长因子单克隆抗体Bevacizumab的毒性观察

目的 观察不同剂量的抗血管内皮生长因子单克隆抗体Bevacizumab玻璃体腔注射后对兔眼角膜、房角、视网膜组织结构和功能的影响。 方法 24只健康新西兰大白兔分成3组，每组兔眼右眼分别注射Bevacizumab 1.25、2.50、5.00 mg；左眼为对照眼，注射相同体积的0.9％生理盐水。注射药物前后裂隙灯显微镜及直接检眼镜检查眼前段和眼底，监测眼压。注药前以及注药后1、4、8周行闪光视网膜电图（ERG）检查。8周时行角膜内皮计数后，摘除眼球行光学显微镜及透射电子显微镜检查。 结果 3组兔眼注射药物前后各时间点眼压、角膜内皮计数、ERG的a、b波振幅差异无统计学意义（P＞0.05）。光学显微镜检查，3组兔 眼角膜、房角、视网膜结构无明显变化。透射电子显微镜检查，视网膜超微结构亦无明显变化。 结论 玻璃体腔内注射1.25～5.00 mg Bevacizumab对正常兔眼组织没有明显毒性。 （中华眼底病杂志，2008，24：189-192）     

外源性可溶性促红细胞生成素受体对正常大鼠视网膜神经元存活的影响

目的观察玻璃体腔注射外源性可溶性促红细胞生成素受体（EPOsR）对视网膜神经元存活的影响。方法30只SD鼠随机分为正常对照组、PBS组、EPOsR 2ng组、EPOsR 20ng组、EPOsR 200ng组，每组6只（12只眼）。后4组玻璃体腔内分别注射5μL PBS，2、20、200ng EPOsR。注射前记录闪光视网膜电图（FERG），注射后3d再次进行FERG检查及视网膜神经元TUNEL凋亡原位检测，注射后7d进行光学显微镜和透射电镜检查。结果注药前后各组a波、b波的潜伏期及振幅差异无统计学意义（P〉0．05），震荡电位（OPs）的P4潜伏期和各子波总振幅差异亦无统计学意义（P〉0．05）；全层视网膜神经元TUNEL凋亡原位检测未见凋亡细胞；光学显微镜和透射电镜检查均未见明显的水肿、空泡状变性等组织病理学改变。结论玻璃体腔注射200ng以下剂量的外源性EPOsR不影响正常状态下视网膜神经元的存活。     

维甲酸纳米粒对视网膜毒性作用的实验分析

目的分析维甲酸纳米粒对兔视网膜毒性作用的影响因素。方法30只青紫蓝兔随机分为5组，包括正常组、10μg／mL、20μg／mL维甲酸纳米粒组、15μg／mL、10μg／mL丙酮组。分别于玻璃体腔注药后7、14、28d用检眼镜观察眼底变化，并行双眼视网膜电图(ERG)检查，摘除眼球行组织学观察。结果7d时，20μg／mL维甲酸组及15μg/mL丙酮组出现视网膜神经节细胞(RGCs)的空泡样变，但在14d时恢复正常。其余各组视网膜无明显组织学变化。在各组实验中未发现ERG的明显变化。结论20μg／mL维甲酸纳米粒玻璃体腔注射对视网膜是安全的，制剂中质量浓度≤10μg／mL的丙酮残留不会埘兔视网膜产生毒性作用。     

苦参碱聚乳酸微球的缓释性和玻璃体腔注射的安全性研究

目的研究苦参碱聚乳酸微球（MAT-PLA-MS）的缓释性和玻璃体腔注射的安全性。方法透射电镜观察MAT—PLA—MS的形态,紫外分光光度法观测其体外释放情况。玻璃体腔彩色照相记录其分解过程,裂隙灯显微镜、间接检眼镜、视网膜电图（ERG）、光学显微镜和透射电镜观察不同剂量组的苦参碱游离药物和MAT—PLA—MS在注药后不同时间点对眼组织的影响。结果MAT—PLA—MS的平均粒径为2．28μm,载药量为6．17％。体外释放672h,累积释放百分率为87．93％,缓释作用明显。MAT—PLA—MS在玻璃体腔内随时间延长表现为逐渐降解的过程。游离药物各剂量组和载药微球各剂量组在玻璃体腔注射后各时间点裂隙灯显微镜和间接检眼镜检查均未见异常。游离药物4mg组注药后1dERGb波振幅下降。组织病理学检查表明,游离药物4mg组在注药后1d开始出现视网膜毒性反应,载药微球6mg组在注药7d后出现轻微的视网膜毒性反应。结论MAT—PLA—MS具有明显的缓释效果,安全剂量较游离药物大,有望成为一种理想的防治增生性玻璃体视网膜病变的给药系统。     

环孢素A壳聚糖纳米微粒防治增生性玻璃体视网膜病变

目的评价环孢素A（CsA）壳聚糖纳米微粒抑制增生性玻璃体视网膜病变（PVR）的有效性和安全性。方法20只健康中华大耳白兔制作的PVR动物模型随机分为4组：A组玻璃体腔内注入0．1mL平衡液，B组玻璃体腔内注入0．1mL壳聚糖溶液（含壳聚糖2mg），C组玻璃体腔内注入0．1mL CsA溶液（含CsA0．1mg），D组玻璃体腔内注入0．1mLCsA壳聚糖纳米粒（含CsA0．1mg）。以检眼镜、电生理、光镜和电镜观察视网膜变化情况。结果玻璃体腔注药2周及4周后D组PVR等级均明显较A、B、C三组轻，组间差异具有统计学意义（P〈0．05）；而A组与B组、B组与C组之间比较差异无统计学意义（P〉0．05）。D组注药前与注药后4周暗适应闪光ERGb波振幅的差异无统计学意义（P〉0．05）；D组注药后视网膜组织病理及超微结构未发现明显异常。结论一次性兔眼玻璃体腔注入CsA壳聚糖纳米微粒（含CsA0．1mg）能明显抑制或延缓PVR的发生，并具有生物相容性及安全性。     

玻璃体腔注射乳酸环丙沙星对视网膜 影响的研究

目的探讨玻璃体腔注射乳酸环丙沙星治疗方法对视网膜组织的安全性。方法24只兔随机分为4组，每组6只。玻璃体腔内分别注入0.1 ml不同浓度的乳酸环丙沙星，浓度分别为：2 500 、5 000、10 000 μg/ml；对照组注射生理盐水0.1 ml。手术后观察眼底表现，分别行光学显微镜、透射电子显微镜等组织学检查和视网膜电图（ERG）视网膜功能检查。结果250、500 μg组光学显微镜检查结果未见异常，超微结构大致正常；1 000 μg 组光学显微镜下可见视网膜内外核层排列不规则，神经节细胞水肿变性或脱失，透射电子显微镜下可见超微结构改变。视网膜功能检查显示，各组ERG的a～b波波幅注药前后无明显差别。结论玻璃体腔注射国产乳酸环丙沙星安全、抗菌谱广，500 μg以下是较为安全的眼内应用剂量。(中华眼底病杂志,2005,21:180-182)     

金雀异黄素对视网膜中央静脉阻塞动物模型中闪光视网膜电图的影响

目的评价金雀异黄素（Gen）对兔视网膜中央静脉阻塞（CRVO）后视网膜细胞功能下降是否具有改善作用。方法采用氩激光直接光凝法封闭兔眼视网膜静脉建立CRVO模型成功后1周,将兔分为两组：Gen治疗组6只和DMSO组6只。Gen治疗组兔连续4天玻璃体腔内注射浓度为150μmol／l的Gen 0．1ml,DMSO组兔连续四天玻璃体腔内注射DMSO0．1ml。兔光凝前、光凝后1周、2周行闪光视网膜电流图检查（flash electrorefinogram,FERG）测定视网膜细胞功能。结果（1）激光封闭视网膜静脉可建立兔CRVO模型;（2）Gen治疗组FERG—a、FERG—b波潜伏期较用药前明显缩短（P〈0．05）,DMSO组的FERG与用药前无统计学差异。结论激光封闭致兔视网膜中央静脉阻塞的动物模型是成功的,Gen可改善部分视网膜功能。     

曲安奈德玻璃体内注射对视网膜的影响

目的研究曲安奈德（TA）玻璃体内注射的不同剂量和有无赋形剂对视网膜的影响。方法纯种新西兰白兔32只，随机分成4组行TA玻璃体内注射。第1组为去赋形剂的4 mg TA组，第2组为去赋形剂的25 mg TA组，第3组为含赋形剂的4 mg TA组，第4组为含赋形剂的25 mg TA组。每只动物注药前及注药后1周、1、2个月时行视网膜电图（ERG）检查，注药2个月后处死动物，摘除眼球行光学和电子显微镜检查。结果各组兔眼注药前后各时间点ERG潜伏期无明显变化，但含赋形剂组注药后ERG振幅较注药前降低，差异有统计学意义(P<0.01)；光学和电子显微镜检查显示含赋形剂组视网膜有不同程度的组织结构损害。结论TA玻璃体内注射时，≤25 mg的无赋形剂TA对视网膜形态和功能无影响；赋形剂的存在可导致视网膜功能和形态改变。(中华眼底病杂志,2005,21:229-232)     

双氯酚酸钠玻璃体内应用对视网膜结构和功能的影响

目的 了解非甾体类抗炎药物双氯酚酸钠（diclofenac sodium,DFS)玻璃体内注射对视网膜的毒性作用，探索眼内应用DFS的安全剂量范围。方法 28只健康成年大耳白兔，随机分为7组，分别于每组右眼玻璃体内注入4、5、6、7、8、9、10mg/ml的DFS溶液0.1ml，左眼为对照组。注药前及注药后1、3、7、14、21、28d分别行双眼视网膜电图（electroretinogram,ERG)检查。注药后10、28、30d分别摘除眼球行光学显微镜和透射电镜检查。结果 注药剂量0.4、0．5mg组ERG明、暗适应b波波幅比率与注药前相比差异无显著意义，透射电镜及光学显微镜检查均未见组织结构有明显异常。0.6mg组在注药后1d ERG明适应b波波幅比率较注药前明显下降（P＜0．05），注药后3d开始恢复，至注药后14d已达注药前水平（P＞0．05），光学显微镜及透射电镜检查显示视网膜组织已出现水肿等可逆改变，部分仍维持正常结构。0.7-1.0mg组ERG b波波幅比率与注药前相比明显下降（P＜0．05），且不能恢复，光学显微镜及透射电镜检查显示视网膜各层结构损伤，在注药后10、30d均可见到细胞核染色质浓缩集聚、细胞坏死等不可逆改变。结论 DFS玻璃体内注射的最大安全剂量不得超过0.6mg。当注药剂量大于或等于0.7mg时，对视网膜各层结构产生毒性，主要表现为锥、杆细胞的不可逆损害。     

Comparison of Each Retinal Layer Thicknesses between Eyes with Central Retinal Vein Occlusion and Normal Contralateral Eyes

PurposeTo evaluate the difference in each retinal layer thickness in central retinal vein occlusion (CRVO) with resolved macular edema after intravitreal antivascular endothelial growth factor injection and normal contralateral eyes..MethodsPatients with ischemic and nonischemic CRVO whose macular edema resolved after intravitreal antivascular endothelial growth factor injections and did not recur for at least 6 months, and a normal contralateral eye were enrolled. Each retinal layer thickness between CRVO and normal contralateral eyes was compared according to Early Treatment Diabetic Retinopathy Study subfields using spectral domain optical coherence tomography.ResultsThe thicknesses of outer nuclear layer, photoreceptor layer, and retinal pigment epithelium in central ring, ganglion cell layer, inner plexiform layer, outer nuclear layer, and photoreceptor layer in the inner ring, and ganglion cell layer in the outer ring of CRVO eyes were significantly thinner than those of normal contralateral eyes (all p < 0.05). Whereas, inner nuclear layer and outer plexiform layer thicknesses in central ring of CRVO eyes were 23.86 ± 8.8 and 25.76 ± 7.6 μm, respectively, which was significantly thicker than those of normal contralateral eyes (19.52 ± 7.7 and 22.76 ± 6.5 μm; p = 0.019 and p = 0.043, respectively). Additionally, the mean best-corrected visual acuity of CRVO eyes were significantly correlated with photoreceptor layer thickness in central ring (p = 0.005).ConclusionsIn CRVO eyes with resolved macular edema, the outer retinal layers were thinner as well as inner retinal layers, whereas inner plexiform layer and outer nuclear layer were thicker than normal fellow eyes. Additionally, photoreceptor layer thickness in foveal area had a significant impact on visual acuity in CRVO.     

Protective effect of hepatocyte growth factor against degeneration of the retinal pigment epithelium and photoreceptor in sodium iodate-injected rats

PURPOSE: To investigate the possible protective effect of hepatocyte growth factor (HGF) against degeneration of photoreceptors and retinal pigment epithelium (RPE) in vivo. METHODS: Sprague-Dawley (SD) rats received an intravitreal injection of HGF in the right eye. The left eye was injected with vehicle as a control. Two days after the intravitreal injections, rats were administered 40 mg/kg of sodium iodate (NaIO3) intravenously. Scotopic ERGs were elicited by different stimulus intensities with a maximum luminance of 0.84 log cds/m2. To evaluate RPE function, the azide response was evoked by intravenous injection of 0.1 mg sodium azide. These electrophysiological measurements were conducted on days 4, 7, 14, and 28 after the NaIO3 injections. After recording ERGs or azide response, animals were sacrificed for quantification of the histological change and immunohistochemical analysis using antibodies against RPE 65. RESULTS: The threshold for the scotopic b-wave was significantly lower in HGF-treated eyes than in untreated control eyes (p < 0.005), and maximum b-wave amplitudes (Vbmax) were significantly larger in HGF-treated eyes (p < 0.05) across all experimental time points after NaIO3 injection. Azide response amplitudes were significantly larger in the HGF-treated eyes than in the untreated eyes (p < 0.05). The structure of the outer retina was preserved to a greater degree in the HGF-treated eyes than in the untreated eyes (p < 0.05). Immunohistochemical analysis demonstrated that irregular alignment of the outer nuclear layer was confined to the retinal area that was not stained with RPE 65. CONCLUSIONS: Our results indicated that an intravitreal injection of HGF provided significant protection against degeneration of the photoreceptor and RPE induced by systemic administration of NaIO3. This suggests that HGF could be used as a therapeutic agent for degeneration of photoreceptors as well as RPE.     

兔玻璃体内注射聚N-异丙基丙烯酰胺-聚氧化乙烯纳米粒的眼内毒理学效应

目的:评估玻璃体腔内注射新型缓释给药载体聚N-异丙基丙烯酰胺-聚氧化乙烯(PNIPAAm-PEO)纳米粒的眼内毒理学效应。方法:玻璃体腔注射不同浓度(1mg/0.1mL,2mg/0.1mL,3mg/0.1mL,4mg/0.1mL)的PNIPAAm-PEO纳米稀释液后于不同时间点行裂隙灯、检眼镜、视网膜电图以及组织病理学检测。对照组注射0.1mL无菌生理盐水。将所用不同浓度稀释液局部点眼,观察局部组织的刺激反应。结果:兔眼角结膜对检测浓度范围内的PNIPAAm-PEO有良好耐受性,眼部无刺激症状。玻璃体腔内注射1mg和2mg组未见明显视网膜毒性反应。3mg组眼底检查无异常,ERG-b波1~3d下降幅度>30%,第7~14d略有恢复;第14d光镜下视网膜部分感光细胞外节间隙增宽,外丛状层以内结构空泡变性,细胞排列正常;电镜下各层均有较明显的结构改变,广泛的细胞水肿和空泡变性,细胞间隙增宽,感光细胞膜盘结构基本正常。4mg组ERG-b波波幅下降>30%;第1~14d组织病理学观察均有明显视网膜结构破坏,广泛空泡变性,部分感光细胞的盘膜崩解,层状结构紊乱、模糊不清。结论:PNIPAAm-PEO纳米粒的眼部耐受性良好,具有用作眼部给药载体的潜力,但大剂量使用时应注意眼部安全性问题。     

Functional and morphological effects of β-estradiol in eyes with N-methyl-D-Aspartate-induced retinal neurotoxicity in rats

Glutamate-mediated excitotoxicity, mainly induced by N-methyl-d-aspartate (NMDA) receptors, is known to cause retinal ganglion cell death in retinal ischemia, glaucoma, and several other retinal diseases. We evaluated the effects of β-estradiol (E2) against a single intravitreal injection of NMDA using a functional and morphological approach. Male rats were randomly divided into 3 treatment groups: (1) Control; (2) NMDA (intravitreal injection of 5 mM NMDA); and (3) NMDA + E2 (intravitreal injection of 5 mM NMDA and pretreatment with subcutaneous E2 implantation). Seven days after NMDA injection, full-field electroretinograms (ERGs) and quantitative morphological analyses using transverse sections of the retina were conducted. In the NMDA group, full-field ERGs showed reductions in the amplitudes of the negative-scotopic threshold response, rod response b-wave, oscillatory potentials, flicker response second b-wave and cone response b-wave. Morphological evaluations of transverse sections of the retina demonstrated a reduction in the thickness of the inner plexiform layer, increases in the thickness of the outer plexiform and outer nuclear layers, and a loss of cells in the ganglion cell layer. In the NMDA + E2 group, pretreatment with E2 prevented the aggravations in the amplitudes of the ERGs except for oscillatory potential 2 (OP2); however, no morphological differences between the NMDA and NMDA + E2 groups were seen. These findings indicate that E2 can protect retinal function against NMDA-induced neurotoxicity. In addition, these indications suggested that the effect of E2 may have therapeutic benefits in NMDA related diseases, such as retinal ischemia and glaucoma.     

Effects of indocyanine green injection on the retinal surface and into the subretinal space in rabbits

PURPOSE: To evaluate the effects of indocyanine green (ICG) injection on the retinal surface and into the subretinal space of rabbit eyes. METHODS: Twenty-two Dutch-belted rabbits underwent two-port vitrectomy followed by injection of ICG (5 mg/mL) on the retinal surface and into the subretinal space. Balanced salt solution (BSS) was also injected subretinally. The locations where ICG was delivered (both epiretinal and subretinal) were exposed to light from an endoilluminator for 7 minutes. The animals were examined at 1, 7, and 14 days after surgery. The eyes were studied by fluorescein angiography as well as light and electron microscopy. RESULTS: No damage was observed after epiretinal ICG injection, but subretinal ICG injection resulted in damage to the outer nuclear layer, photoreceptor inner and outer segments, and retinal pigment epithelium. This damage was more severe with longer follow-up. Control experiments without ICG, in which balanced salt solution was injected into the subretinal space or light was delivered on the epiretinal surface, demonstrated only damage to the photoreceptor outer segments. CONCLUSION: Subretinal delivery of ICG (5 mg/mL) in rabbits induces retinal pigment epithelium, photoreceptor inner and outer segment, and outer nuclear layer damage. These mechanisms of damage may explain the retinal pigment epithelium changes that are sometimes seen after ICG-assisted internal limiting membrane peeling in humans.     

抗血管内皮生长因子bevacizumab兔眼玻璃体腔重复注射的安全性研究

目的　观察抗血管内皮生长因子bevacizumab（商品名Avastin）兔眼玻璃体腔重复注射的眼内安全性。方法 14只青紫兰兔分为3组,其中12只兔的右眼设为实验组,左眼设为实验对照组,2只兔为正常对照组。实验组右眼予以25 mg/ml的bevacizumab玻璃体腔注射,实验组根据不同注射剂量分为2.5、5.0 mg 2个剂量组,左眼分别注射等剂量0.9%生理盐水作为实验对照。玻璃体腔共注射3次,每次间隔2周。每次注射前、注射后2 d,第3次注射后1、4周采用裂隙灯显微镜、+90 D前置镜、B型超声、超生生物显微镜（UBM）、光相干断层扫描（OCT）进行临床指标观察,视网膜电图（ERG）和闪光视觉诱发电位（F-VEP）进行视网膜功能检测。第3次注射完毕后1、4周分别摘取眼球进行病理组织学观察和凋亡细胞检测。结果　所有实验眼和实验对照眼均未见明显炎症反应,各组眼底未见明显异常,玻璃体无混浊、出血。B型超声、UBM和OCT检查均未见明显改变。注射前后不同剂量实验组与实验对照组、正常对照组眼压、前房闪辉计数比较,差异均无统计学意义(P＞0.05)。不同剂量实验组与注射前、实验对照组、正常对照组最大反应ERG a、b波比较,差异均无统计学意义(P＞0.05)。注射前后,F-VEP N₁波潜伏期和P1波振幅各组差异均无统计学意义(P＞0.05)。光学显微镜观察发现,不同剂量实验组第3次注射后1 周玻璃体腔可见少量炎症细胞,注射后第4周未见炎症细胞;实验对照组和正常对照组注射前后视网膜组织形态未见明显改变。5.0  mg实验组第3次注射后1周电子显微镜下可见炎症细胞,个别视细胞细胞核呈空泡样改变,其余未见明显异常。凋亡细胞计数显示,第3次注射后1周,5.0 mg实验组与2.5、5.0 mg实验对照组（Z=0.227）和正常对照组（Z=1.341）组间凋亡细胞数量比较,差异均有统计学意义（P＜0.01）,第3次注射后4周,各组差异无统计学意义（χ2=4.826,P>0.05）。结论　5.0 mg bevacizumab在兔眼玻璃体腔多次注射视网膜有一定轻微毒性反应。     

A primate model of macular cyst

Perfluoropropane (C3F8) was injected into nine eyes of six cynomolgus monkeys. In all nine eyes, macular changes consistent with the development of a macular cyst were noted within 3 months after injection. On fluorescein angiography, there was no evidence of retinal vascular leakage associated with the macular cysts. Histopathologic evaluation of six eyes demonstrated microcystic changes throughout the perifoveal inner nuclear layer. These coalesced into larger cystic spaces in the outer plexiform layer of the central macula. These macular changes are previously unreported in patients or monkeys undergoing intravitreal injection of expansile gases. This model for macular cysts may be helpful in evaluating the pathogenesis and role of interventional strategies in patients with cystoid macular edema.     

Intravitreal toxicity of garenoxacin

PURPOSE: To assess the retinal toxicity of varying concentrations of intravitreally injected garenoxacin. METHODS: Twenty eyes of 20 New Zealand albino rabbits were used for this study. The animals were anesthetized with ketamine (35-50 mg/kg) and xylazine (3-5 mg/kg). Garenoxacin was titrated using distilled water to the following concentrations: 4,000, 2,000, 1,000, 400, 200, and 100 microg/0.1 mL. Each concentration was injected intravitreally (0.1 mL) into three rabbit eyes. Three control eyes were injected with 0.1 mL of balanced saline solution. All animals were examined before and after injection by indirect ophthalmoscopy and slit-lamp biomicroscopy. Electroretinography was performed on all animals before intravitreal injection and 14 days after injection. The animals were examined by indirect ophthalmoscopy and slit-lamp biomicroscopy before they were killed; the eyes were enucleated and examined with light microscopy. RESULTS: No electroretinographic changes or signs of retinal toxicity by slit-lamp examination, indirect ophthalmoscopy, or light microscopy were seen in any eyes 14 days after intravitreal injection of garenoxacin (< or =4,000 microg/0.1 mL). CONCLUSIONS: Garenoxacin injected intravitreally appeared safe at concentrations of < or =4,000 microg/0.1 mL.     

小胶质细胞介导的炎症反应在衣霉素所致的小鼠视网膜损伤中的作用

目的　探讨小胶质细胞介导的炎症反应在衣霉素所致的小鼠视网膜损伤中的作用。方法　取50只C57/BL6J小鼠,随机分为5组,每组10只;DMSO组给予小鼠玻璃体内注射DMSO溶液1 μL;衣霉素低剂量组给予小鼠玻璃体内注射50 mg?L^-1衣霉素1 μL,衣霉素中剂量组注射100 mg?L^-1衣霉素1 μL,衣霉素高剂量组注射150 mg?L^-1衣霉素1 μL;对照组给予相同条件下喂养。采取小鼠玻璃体内注药建模后,分别进行OCT检查及HE染色观察小鼠视网膜组织形态改变;进行闪光视网膜电图检测评估视网膜视功能;免疫荧光染色及Western blot检测视网膜中Iba1及IL-6的表达情况。结果　与对照组相比,衣霉素低剂量组视网膜各层结构紊乱,视网膜外层呈波浪状改变,并出现细胞核排列紊乱;衣霉素中剂量组及高剂量组视网膜各层结构紊乱更加明显,并出现神经上皮与色素上皮的浅层脱离,IS/OS层及外丛状层消失。造模后第7天,闪光视网膜电图结果显示:对照组与DMSO组a波及b波振幅无差异;与对照组相比,衣霉素低剂量组、中剂量组及高剂量组a波、b波振幅下降,且呈剂量依赖性,其中a波振幅下降更为明显,差异均有统计学意义（均为P<0.05）。与对照组相比,衣霉素低剂量组、中剂量组及高剂量组视网膜内核层及外核层中Iba1表达量明显增多,且呈剂量依赖性（均为P<0.05）;IL-6视网膜中呈现与Iba1相似的表达。结论　小胶质细胞参与衣霉素所致的小鼠视网膜损伤过程,并产生相关炎症因子引起视网膜功能及结构改变。