本文選題：青光眼 + 微球��； 參考：《復(fù)旦大學(xué)》2012年博士論文

【摘要】：研究目的：隨著微球誘導(dǎo)的小鼠高眼壓模型在眼科基礎(chǔ)研究中被廣泛地接受和采用,本研究利用該模型檢測各種目前臨床上常用的青光眼藥物的降眼壓和視神經(jīng)保護(hù)作用,用于進(jìn)一步探究該模型在未來青光眼新藥篩選中的應(yīng)用潛力,并嘗試使用頻域光學(xué)相干斷層掃描無創(chuàng)性地測量小鼠高眼壓模型中的視網(wǎng)膜厚度改變。 材料和方法：在氯胺酮(120mg/kg)和甲苯胺噻嗪(12mg/kg)腹腔麻醉下,采用單側(cè)前房注射2微升聚苯乙烯微球懸浮液(5.0×106微球/毫升)的方法在成年C57BL/6J小鼠上建立高眼壓模型。比較常用的幾種青光眼降眼壓藥物(0.5%馬來酸噻嗎洛爾滴眼液、0.15%酒石酸溴莫尼定滴眼液、1%布林佐胺滴眼液、2%鹽酸毛果蕓香堿滴眼液和0.005%拉坦前列素滴眼液)在這個高眼壓模型中的作用。使用TonoLab眼壓計監(jiān)測眼壓變化來評價藥物的短期和長期降眼壓作用。通過對視網(wǎng)膜神經(jīng)節(jié)細(xì)胞和視神經(jīng)軸突計數(shù)的方法對視神經(jīng)損害進(jìn)行定量分析,比較青光眼藥物的視神經(jīng)保護(hù)作用。同時采用頻域光學(xué)相干斷層掃描技術(shù)配合自主開發(fā)的圖像分析軟件測量小鼠視網(wǎng)膜神經(jīng)節(jié)細(xì)胞復(fù)合體的厚度(包括視網(wǎng)膜神經(jīng)纖維層、視網(wǎng)膜神經(jīng)節(jié)細(xì)胞層以及內(nèi)叢狀層),利用該厚度變化比較這青光眼藥物的治療作用。同時分析視網(wǎng)膜神經(jīng)節(jié)細(xì)胞復(fù)合體厚度變薄率和視網(wǎng)膜神經(jīng)節(jié)細(xì)胞丟失率之間的關(guān)系。P0.05被認(rèn)為具有統(tǒng)計學(xué)意義。 結(jié)果：微球注入前房后散布在前房水中,隨后逐漸堆積到房角附近,導(dǎo)致了房水外流通道阻塞。眼壓隨之逐漸升高,在第8天時達(dá)到高峰,并且高眼壓一直維持到第3周或更長時間。微球注射眼的視網(wǎng)膜神經(jīng)節(jié)細(xì)胞和軸突的數(shù)量較對側(cè)眼明顯減少。我們通過單側(cè)前房注射聚苯乙烯微球的方法成功地建立了小鼠高眼壓模型。以抑制房水生成為主要作用機(jī)制的降眼壓藥物(0.5%馬來酸噻嗎洛爾滴眼液、0.15%酒石酸溴莫尼定滴眼液和1%布林佐胺滴眼液)可以有效降低微球?qū)е赂哐蹓耗Ｐ褪蟮难蹓?與對照組相比視網(wǎng)膜神經(jīng)節(jié)細(xì)胞和視神經(jīng)軸突的存活率有明顯改善。同時,頻域光學(xué)相干斷層掃描配合自主開發(fā)的圖像分析軟件可以成功地測量小鼠視網(wǎng)膜神經(jīng)節(jié)細(xì)胞復(fù)合體的厚度。測量結(jié)果發(fā)現(xiàn),與對照組相比,以抑制房水生成為主要作用機(jī)制的三種降眼壓藥物均能明顯降低由高眼壓導(dǎo)致視網(wǎng)膜神經(jīng)節(jié)細(xì)胞復(fù)合體厚度變薄的幅度。然而以促進(jìn)房水外流為主要作用機(jī)制的降眼壓藥物(0.005%拉坦前列素滴眼液和2%鹽酸毛果蕓香堿滴眼液)對微球?qū)е赂哐蹓耗Ｐ褪蟮难蹓簞t完全沒有影響。另外,視網(wǎng)膜神經(jīng)節(jié)細(xì)胞復(fù)合體厚度變薄率與視網(wǎng)膜神經(jīng)節(jié)細(xì)胞丟失率之間有明顯的相關(guān)性。 結(jié)論：前房注射微球的方法可以有效地誘發(fā)小鼠眼壓升高并且發(fā)生青光眼性的視神經(jīng)損害。三種房水生成抑制劑在微球?qū)е滦∈蟾哐蹓耗Ｐ椭芯l(fā)揮了有效地降眼壓和視神經(jīng)保護(hù)作用。該小鼠高眼壓模型是一種房水外流障礙的模型,可有效用于以抑制房水生成為作用機(jī)制的降眼壓新藥的篩選。同時,本研究發(fā)現(xiàn)使用光學(xué)相干斷層掃描測量視網(wǎng)膜神經(jīng)節(jié)細(xì)胞復(fù)合體厚度為檢測青光眼模型小鼠視神經(jīng)損害、評價藥物療效提供了一個新的生物學(xué)指標(biāo)。
[Abstract]:Objective: with the microsphere induced mouse ocular hypertension model is widely accepted and adopted in the basic research of Ophthalmology, this study uses this model to detect the effect of intraocular pressure and optic nerve protection on various current commonly used glaucoma drugs, and to further explore the potential application potential of the model in the screening of new glaucoma drugs in the future. And try to use frequency domain optical coherence tomography to measure retinal thickness in a mouse model of high intraocular pressure.
Materials and methods: a high intraocular pressure model was established in adult C57BL/6J mice by intraperitoneal anesthesia with ketamine (120mg/kg) and toluidine thiazide (12mg/kg), using a unilateral anterior chamber injection of 2 microsphere polystyrene microspheres (5 x 106 microspheres / milliliters). Several common glaucoma lowering drugs (0.5% maleic acid timolol eye drops) were compared. The role of liquid, 0.15% Brimonidine Tartrate Opthealmic Solution, 1% Brinzolamide Eye Drops, 2% pilocarpine eye drops and 0.005% Latanoprost Eye Drops in this high intraocular pressure model. Using the TonoLab tonometer to monitor intraocular pressure changes to evaluate the short-term and long-term depressurized action of the drug. Through the retinal ganglion cells and the optic deity The method of counting the optic nerve was used to analyze the optic nerve damage and to compare the protective effect of the optic nerve in the glaucoma. The thickness of the retinal ganglion cell complex (including the retinal nerve fiber layer, the retinal ganglion) was measured by the frequency domain optical coherence tomography and the self developed image analysis software. The cell layer and the inner plexiform layer were used to compare the therapeutic effect of this glaucoma drug. The relationship between the thickness thinning rate of the retinal ganglion cell complex and the retinal ganglion cell loss rate (.P0.05) was considered statistically significant.
Results: the microspheres were scattered in the anterior chamber water after the injection of the anterior chamber, and then gradually accumulated near the corner of the room, which resulted in the obstruction of the aqueous Exodus channel. The intraocular pressure increased gradually and reached the peak at eighth days, and the high intraocular pressure remained to third weeks or longer. The number of retinal ganglion cells and axons in the microsphere injection eye was more than the opposite eye. We successfully established a model of high intraocular pressure in mice by injecting polystyrene microspheres into one side of the anterior chamber. In order to inhibit the main mechanism of the aqueous humor of the aqueous humor (0.5% Timolol Maleate Eye Drops, 0.15% Brimonidine Tartrate Opthealmic Solution and 1% Brinzolamide Eye Drops), we can effectively reduce the height of the microspheres. The intraocular pressure of the intraocular pressure model rats was significantly improved compared with the control group. Meanwhile, the frequency domain optical coherence tomography combined with the self developed image analysis software could successfully measure the thickness of the retinal ganglion cell complex in mice. Three kinds of intraocular pressure lowering drugs can significantly reduce the thickness of the retinal ganglion cell complex caused by high intraocular pressure. However, the anti ophthalmic drugs (0.005% Latanoprost Eye Drops and 2% pilocarpine eye drops), which are the main mechanism of promoting aqueous Exodus (0.005% and 2% hairy rutin eye drops), In addition, there is a significant correlation between the thickness thinning rate of the retinal ganglion cell complex and the loss rate of retinal ganglion cells.
Conclusion: the injection of microspheres in the anterior chamber can effectively induce the increase of intraocular pressure in mice and the occurrence of glaucomatous optic nerve damage. Three kinds of aqueous humor inhibitors play an effective role in reducing intraocular pressure and optic nerve protection in the model of high intraocular pressure in mice. The model of high ocular pressure in mice is a model of aqueous humor disorder. At the same time, the use of optical coherence tomography (optical coherence tomography) to measure retinal ganglion cell complex thickness can be used to detect optic nerve damage in glaucoma model mice and to provide a new biological index for evaluating the efficacy of the drug.

【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2012
【分類號】：R775.9

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 楊帆;吳玲玲;郭秀娟;楊麗萍;李穎;吳樂萌;王冬梅;;青光眼動物模型DBA/2J小鼠的眼部特征及組織學(xué)觀察[J];眼科研究;2010年02期

2 吳慧娟;鮑永珍;任澤欽;侯憲如;劉國棟;;頻域光學(xué)相干斷層掃描在視網(wǎng)膜神經(jīng)纖維層厚度測量中的應(yīng)用[J];眼科研究;2010年05期

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本文編號：1830021