本文選題：鞏膜 + 膠原交聯(lián)��； 參考：《首都醫(yī)科大學(xué)》2013年博士論文

【摘要】：目的：盡管近視的發(fā)生機(jī)制至今未明，但是研究普遍認(rèn)為進(jìn)行性近視的發(fā)生是由于各種先天和或后天的因素導(dǎo)致鞏膜在眼內(nèi)壓的作用下變薄，進(jìn)而造成眼球被動拉長引起的。鞏膜的紫外光-核黃素膠原交聯(lián)術(shù)是一項(xiàng)能增強(qiáng)鞏膜自身生物力學(xué)強(qiáng)度的新技術(shù)。本研究旨在進(jìn)一步評價(jià)目前國際研究中普遍采用的鞏膜膠原交聯(lián)方案在應(yīng)用于新鮮尸眼和兔眼鞏膜時(shí)的有效性和安全性。 方法：本研究采用單向拉伸試驗(yàn)來評估該鞏膜膠原交聯(lián)方案增加生物力學(xué)強(qiáng)度的有效性。首先檢測人眼鞏膜紫外光-核黃素交聯(lián)術(shù)的生物力學(xué)特性，將6只新鮮尸眼隨機(jī)分為交聯(lián)和非交聯(lián)對照組，分別進(jìn)行赤道部和后極部鞏膜試件的應(yīng)力-應(yīng)變檢測。接著，將20只新西蘭兔隨機(jī)分為4組，分別對非交聯(lián)對照組、術(shù)后1周組、術(shù)后1月組和術(shù)后3月組的兔眼鞏膜試件進(jìn)行拉伸檢測。在比較兔眼和人眼鞏膜術(shù)后生物力學(xué)效果時(shí)，以應(yīng)變?yōu)?%時(shí)的楊氏模量作為指標(biāo)進(jìn)行比較。在鞏膜膠原交聯(lián)安全性的研究中，本研究采用細(xì)胞脫氧核苷酸末端轉(zhuǎn)移酶技術(shù)（Terminal deoxynucleotidyl transferase dUTP nick-end labeling，TUNEL）檢測和電子顯微鏡技術(shù)（transmission electron microscopy，TEM）對6只新鮮尸眼赤道部鞏膜進(jìn)行檢測評價(jià)，檢驗(yàn)鞏膜交聯(lián)和未交聯(lián)對人眼視網(wǎng)膜組織病理學(xué)的影響。隨后，本研究對25只新西蘭兔在鞏膜交聯(lián)術(shù)前、術(shù)后1周、1月和3月時(shí)的暗適應(yīng)視網(wǎng)膜電圖進(jìn)行檢測，并采用TUNEL染色和電子顯微鏡技術(shù)對兔眼視網(wǎng)膜組織病理學(xué)的影響進(jìn)行觀察和分析。 結(jié)果：新鮮尸眼和兔眼鞏膜的厚度在交聯(lián)前后無統(tǒng)計(jì)學(xué)差別。兔眼和人眼鞏膜的應(yīng)力-應(yīng)變曲線呈非線性變化，符合σ=Aexp(B*ε)指數(shù)方程。兔眼和尸眼的鞏膜生物力學(xué)強(qiáng)度在交聯(lián)后均得到增強(qiáng)。交聯(lián)術(shù)后人眼赤道部鞏膜楊氏模量是非交聯(lián)赤道部鞏膜的1.85倍，是交聯(lián)術(shù)后人眼后極部鞏膜楊氏模量的1.15倍；兔眼赤道部鞏膜的楊氏模量在交聯(lián)術(shù)后1周、1月和3月時(shí)分別增加到原來的297%,253%and163%；。經(jīng)過鞏膜交聯(lián)的新鮮尸眼視網(wǎng)膜在TUNEL染色檢測和電子顯微鏡檢測中與非交聯(lián)眼視網(wǎng)膜沒有明顯區(qū)別。交聯(lián)術(shù)后1周和1月時(shí)兔眼暗適應(yīng)ERG峰值有明顯下降。尤其是Dark-adapted0.01ERG（1周，P=.001；1月，P=.022）和Dark-adapted3.0ERG（1周，P=.047；1月，，P=.035）的b波。而術(shù)后3月時(shí)的兔眼暗適應(yīng)ERG峰值與術(shù)前沒有統(tǒng)計(jì)學(xué)差異。交聯(lián)術(shù)后1周和1月時(shí)兔眼視網(wǎng)膜中發(fā)現(xiàn)了大量的凋亡細(xì)胞。電子顯微鏡顯示術(shù)后1周時(shí)兔眼視網(wǎng)膜的超微結(jié)構(gòu)出現(xiàn)了異常。 結(jié)論：實(shí)驗(yàn)證明，目前國際上普遍采用的鞏膜交聯(lián)研究方案能夠明顯增強(qiáng)兔眼和人眼鞏膜的生物力學(xué)強(qiáng)度。然而，該鞏膜交聯(lián)方案可能并不安全，尤其是會引起兔眼視覺功能的慢性損傷，并可引起其視網(wǎng)膜細(xì)胞的凋亡。
[Abstract]:Objective: although the mechanism of myopia is still unknown, it is generally believed that the occurrence of progressive myopia is caused by various congenital and acquired factors, which result in sclera thinning under intraocular pressure, and then cause passive lengthening of the eyeball. Ultraviolet-riboflavin collagen crosslinking is a new technique to enhance the biomechanical strength of sclera. The purpose of this study was to evaluate the efficacy and safety of the scleral collagen crosslinking protocol which has been widely used in international studies in the sclera of fresh cadaver eyes and rabbit eyes. Methods: uniaxial tensile test was used to evaluate the effectiveness of the scleral collagen crosslinking regimen in increasing biomechanical strength. The biomechanical properties of scleral ultraviolet-riboflavin crosslinking were investigated. Six fresh eyes were randomly divided into cross-linked and non-cross-linked control groups. The stress-strain tests were performed in the equatorial and posterior polar scleral specimens respectively. Then, 20 New Zealand rabbits were randomly divided into 4 groups, and the scleral specimens of non-crosslinked control group, postoperative 1 week group, postoperative 1 month group and postoperative 3 months group were tested for stretching. The biomechanical effects of sclera surgery in rabbits and human eyes were compared with the Young's modulus at strain of 8. In the study of the safety of collagen crosslinking in sclera, terminal deoxynucleotidyl transferase dUTP nick-end labeling technique and transmission electron microscopy were used to detect and evaluate the equatorial sclera of 6 fresh cadavers. The effects of scleral crosslinking and uncrosslinking on the histopathology of human retina were examined. Subsequently, 25 New Zealand rabbits were examined for electroretinogram of dark adaptation before scleral crosslinking, 1 week, 1 month and 3 months postoperatively. The effects of Tunel staining and electron microscopy on the histopathology of rabbit retina were observed and analyzed. Results: there was no significant difference in scleral thickness between fresh cadaver eyes and rabbit eyes before and after crosslinking. The stress-strain curve of sclera of rabbit and human eyes showed nonlinear change, which was in accordance with 蟽 Aexpa B * 蔚) exponential equation. The scleral biomechanical strength of both rabbit and cadaveric eyes was enhanced after crosslinking. The Young's modulus of the equatorial sclera after crosslinking was 1.85 times of that of the non-crosslinked equatorial sclera and 1.15 times of that of the posterior pole sclera. The Young's modulus of the equatorial sclera of rabbit eyes increased to 29773 and 1633 at 1 week, 1 month and 3 months after crosslinking, respectively. The retina of fresh cadaveric eyes after scleral crosslinking was not significantly different from that of uncrosslinked eyes in Tunel staining and electron microscopy. At 1 week and 1 month after crosslinking, the peak value of ERG in rabbit eyes decreased significantly. In particular, the b waves of Dark-adapted0.01ERGG (1 week) and Dark-adapted3.0ERG (1 week) and January (P0. 035). However, there was no significant difference between the peak of ERG and the preoperative level of dark adaptation at 3 months after operation. A large number of apoptotic cells were found in the retina of rabbit eyes at 1 week and 1 month after crosslinking. The ultrastructure of the retina of rabbit eyes was abnormal 1 week after operation by electron microscope. Conclusion: the experimental results show that the scleral crosslinking research program widely used in the world can significantly enhance the biomechanical strength of sclera in rabbits and human eyes. However, the scleral crosslinking protocol may not be safe, especially can cause chronic damage of visual function and apoptosis of retinal cells in rabbit eyes.
【學(xué)位授予單位】：首都醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2013
【分類號】：R779.6

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