本文選題：原發(fā)性開角型青光眼 + 眼壓波動��； 參考：《第三軍醫(yī)大學(xué)》2014年博士論文

【摘要】：研究背景 青光眼是一組以視野缺損為特征的視神經(jīng)病變，高眼壓是最重要的危險(xiǎn)因素。當(dāng)前最主要的治療方式是通過各種方法降低眼壓，減慢疾病的進(jìn)程。在原發(fā)性開角型青光眼（primary open-angle glaucoma，POAG）中，小梁網(wǎng)組織發(fā)生病理性改變是主要的致病原因，小梁網(wǎng)組織細(xì)胞外基質(zhì)發(fā)生堆積、小梁柱之間的空間減少、密度增加，小梁網(wǎng)細(xì)胞功能發(fā)生障礙，導(dǎo)致房水流經(jīng)小梁網(wǎng)時(shí)阻力增大，引起了高眼壓。但是到目前為止，導(dǎo)致青光眼小梁網(wǎng)組織發(fā)生病變的原因和機(jī)制仍然未知。 小梁網(wǎng)橋接于鞏膜突和角膜后彈力層之間，由多孔的、扁平的膠原板層構(gòu)成類似海綿狀的結(jié)構(gòu)，小梁細(xì)胞粘附于小梁網(wǎng)的小柱中，中間無血管組織。由睫狀體產(chǎn)生的房水必須經(jīng)過小梁網(wǎng)組織，才能到達(dá)其外側(cè)的蘇氏管。小梁網(wǎng)的管旁組織和蘇氏管的內(nèi)側(cè)是房水流出阻力的主要產(chǎn)生部位，并對眼壓有重要調(diào)節(jié)功能。由于小梁網(wǎng)獨(dú)特的物理位置及組織結(jié)構(gòu)，自分泌和旁分泌是小梁網(wǎng)細(xì)胞對房水阻力調(diào)節(jié)的主要方式。在POAG中，許多細(xì)胞因子、化合物、核苷對房水的流出有不同程度的調(diào)節(jié)作用，并對小梁網(wǎng)的結(jié)構(gòu)產(chǎn)生影響，但是如何觸發(fā)這些物質(zhì)在眼部的釋放還不清楚。 在健康人群中，眼壓存在著生物節(jié)律性波動和日常生活引起的無規(guī)律性波動。由于眼壓的波動和房水的流出，小梁網(wǎng)組織承受著多種形式的生物力。在組織發(fā)育和形態(tài)的維持過程中，生物力對細(xì)胞有重要的調(diào)節(jié)作用，能夠改變組織的結(jié)構(gòu)和功能。研究證實(shí)，原發(fā)性開角型青光眼患者的眼壓波動比健康人群要大得多。小梁網(wǎng)細(xì)胞是一種力學(xué)敏感型細(xì)胞，眼壓大幅波動引起的小梁網(wǎng)組織形態(tài)的變化產(chǎn)生的生物力，同樣會對小梁網(wǎng)細(xì)胞和小梁網(wǎng)組織產(chǎn)生重要的影響。因此，我們推測，早期大幅的眼壓波動可能引起原發(fā)性開角型青光眼小梁網(wǎng)組織病變，成為后期高眼壓癥和青光眼的發(fā)生的一個(gè)重要原因。 為了檢驗(yàn)這一假設(shè)，本課題從以下三個(gè)方面展開研究：1、建立眼壓波動的SD大鼠模型，證實(shí)小梁網(wǎng)組織的改變可源于眼壓波動，而非模型建立過程中的損傷。2、證實(shí)眼壓經(jīng)過一段時(shí)間大幅度的波動后，小梁網(wǎng)的形態(tài)、細(xì)胞外基質(zhì)及肌動蛋白表達(dá)發(fā)生類似于原發(fā)性開角型青光眼小梁網(wǎng)樣的改變。3、探討眼壓波動后引起小梁網(wǎng)細(xì)胞改變的力學(xué)信號傳導(dǎo)通路。 研究目的 通過建立大鼠眼壓波動的動物模型，證實(shí)高眼壓波動能引起小梁網(wǎng)形態(tài)、細(xì)胞外基質(zhì)、肌動蛋白等發(fā)生類似POAG小梁網(wǎng)樣改變，并初步探討導(dǎo)致其改變的小梁網(wǎng)細(xì)胞信號傳導(dǎo)通路。 研究方法 1.對大鼠鞏膜進(jìn)行連續(xù)14天的鉗夾，造成眼壓波動，利用HE染色檢測角膜、鞏膜、視網(wǎng)膜神經(jīng)節(jié)細(xì)胞的損傷情況及小梁網(wǎng)形態(tài)改變情況，ELISA檢測房水IL-6濃度，組化染色檢測CD45陽性細(xì)胞，確定小梁網(wǎng)的形態(tài)改變源于眼壓波動而非機(jī)械損傷；2.對鞏膜進(jìn)行連續(xù)28天的鉗夾造成眼壓波動，利用HE染色檢測角膜、鞏膜、視網(wǎng)膜神經(jīng)節(jié)細(xì)胞的損傷情況及小梁網(wǎng)形態(tài)改變情況，組化染色檢測小梁網(wǎng)細(xì)胞外基質(zhì)蛋白及肌動蛋白表達(dá)變化情況；3.對鞏膜進(jìn)行連續(xù)28天的鉗夾造成眼壓波動，組化染色檢測常規(guī)力信號傳導(dǎo)蛋白的表達(dá)及變化情況。 研究結(jié)果 1.經(jīng)過14天的眼壓波動后，角膜厚度、鞏膜厚度、視網(wǎng)膜神經(jīng)節(jié)細(xì)胞密度沒有發(fā)生改變，房水IL-6濃度無明顯改變，小梁網(wǎng)組織中無CD45陽性細(xì)胞表達(dá)，小梁網(wǎng)密度增加；2.經(jīng)過28天眼壓波動后，角膜厚度、鞏膜厚度、視網(wǎng)膜神經(jīng)節(jié)細(xì)胞密度沒有發(fā)生改變，小梁網(wǎng)肌動蛋白、纖維連接蛋白、層粘連蛋白表達(dá)上調(diào)，小梁網(wǎng)密度增加，眼壓和小梁網(wǎng)厚度無明顯變化；3.經(jīng)過28天的眼壓波動，小梁網(wǎng)組織中Rho A和ERKs表達(dá)上調(diào)，JNK和Beta-catenin無表達(dá)。 結(jié)論 1.眼壓波動模型中小梁網(wǎng)組織發(fā)生的改變源于眼壓波動，而非建立模型過程中的機(jī)械損傷刺激；2.眼壓的波動可以引起小梁網(wǎng)組織中肌動蛋白增加，細(xì)胞外基質(zhì)蛋白沉積，，造成小梁網(wǎng)密度增加等類似于POAG小梁網(wǎng)樣改變；3.眼壓波動引發(fā)Rho A和ERKs等信號蛋白的激活，可能是導(dǎo)致小梁網(wǎng)組織發(fā)生改變的機(jī)制。
[Abstract]:Background of the study

In primary open - angle glaucoma ( POAG ) , there is a major risk factor for glaucoma . In primary open - angle glaucoma ( POAG ) , there is a major cause of disease . In primary open - angle glaucoma ( POAG ) , there is a major cause of disease change . In primary open - angle glaucoma ( POAG ) , the small beam network tissue has a reduced space , the density is increased , and the function of small beam network cells is increased , causing high intraocular pressure .

In POAG , many cytokines , compounds and nucleotides regulate the outflow of aqueous humor to different degrees and have an important effect on the structure of trabecular , but how to trigger the release of these substances in the eye is not clear .

Because of the fluctuation of intraocular pressure and the outflow of aqueous humor , the small beam network tissue is subject to various forms of biological force . In the process of maintaining tissue development and morphology , the biological force plays an important role in regulating the structure and function of tissue .

In order to test the hypothesis , this topic is studied from three aspects : 1 . To establish an SD rat model of intraocular pressure fluctuation . It is proved that the changes of trabecular - net tissue can be derived from the fluctuation of intraocular pressure , rather than the damage in the establishment of the model .

Purpose of study

By establishing an animal model of intraocular pressure fluctuations in rats , it was confirmed that high intraocular pressure fluctuations could cause similar changes in trabecular morphology , extracellular matrix , actin , and the like , similar to that of POAG , and to initially probe into the cell signal transduction pathways leading to changes .

Research Methods

1 . The rat sclera was clamped for 14 days , which caused the fluctuation of intraocular pressure . Using HE staining to detect the damage of cornea , sclera , retinal ganglion cells and the morphological changes of small beam , ELISA was used to detect the concentration of IL - 6 in aqueous humor .
2 . The ocular pressure fluctuation was caused by the continuous 28 - day clamping of sclera , the damage of cornea , sclera and retinal ganglion cells was detected by HE staining , and the morphological changes of trabecular morphology were detected , and the changes of extracellular matrix protein and actin expression were detected by histochemical staining .
3 . The intraocular pressure fluctuation was caused by the continuous 28 - day clamping of sclera , and the expression and change of normal force signal transduction protein were detected by histochemical staining .

Results of the study

1 . After 14 days of intraocular pressure fluctuation , the corneal thickness , scleral thickness , retinal ganglion cell density did not change , the concentration of IL - 6 in aqueous humor was not changed , there was no expression of cd45 - positive cells in trabecular - net tissue , and the trabecular - net density increased ;
2 . After 28 days of intraocular pressure fluctuation , the corneal thickness , scleral thickness and retinal ganglion cell density were not changed . The expression of actin , fibronectin and laminin in trabecular network was up - regulated .
3 . After 28 days of intraocular pressure fluctuation , there was an up - regulation of the expression of rho - A and ERKs in trabecular - net tissue , and no expression was found in the expression of 偽 - catenin and 尾 - catenin .

Conclusion

1 . The change of trabecular - net structure in the model of intraocular pressure fluctuation is caused by the fluctuation of intraocular pressure , rather than mechanical damage stimulation in the process of establishing the model ;
2 . The fluctuation of intraocular pressure can cause the increase of actin and the deposition of extracellular matrix protein in small beam network tissue .
3 . The activation of signal proteins , such as rho A and ERKs , can be caused by intraocular pressure fluctuation , which may be a mechanism that can cause changes in trabecular network tissue .

【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R775.2

【引證文獻(xiàn)】

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