AB020.Inhibition of cyclic-AMP-response element binding protein and its impact on corneal wound healing in vitro and in vivo

Background:The cornea composes the outer surface of the eye and its transparency is required to allow light transmission to the retina.However,because of its position,the cornea is subjected to chemical and mechanical injuries that may lead to blindness.Our studies conducted using the human tissue-engineered cornea(hTEC)as a model provided evidence that the cyclic-AMP-response element binding protein(CREB)pathway is repressed during closure of corneal wounds.Based on these results,we hypothesized that closure of corneal wounds can be enhanced by preventing activation of CREB with the pharmacological inhibitor C646.Our goals were to proceed to the pharmacological inhibition of CREB(I)in vitro using the hTECs as a model,and then(II)in vivo using the rabbit as a model.Methods:The self-assembly approach was used to create hTECs,that were then wounded with an 8-mm diameter biopsy punch to create an epithelial defect.The tissues were then incubated with 10μM of C646(n=8).DMSO was used alone as a negative control(n=4).Closure of the wounds was monitored over a period of 5 days.Besides,the cornea of New Zealand white rabbits was debrided with an ethanol 70%solution to create an epithelial defect of 8-mm diameter.Several concentrations of C646(1,10,100μM et 1 mM)were applied as eye drops 3 times a day for up to 7 days.The wounded corneas(n=4 per concentration)were stained with fluorescein and photographed every day.Results:In vitro pharmacological inhibition of CREB with C646 considerably accelerated wound closure of all treated hTECs(4 days)compared to the control group(7 days).Moreover,the in vivo C646 treatment also accelerated wound healing of the corneas compared to the control group.The most effective concentration of C646 tested was the lowest(1μM),as it considerably enhanced the wound healing process.Conclusions:This study demonstrates that wound healing both in vitro and in vivo can be enhanced by preventing activation of CREB using a pharmacological inhibition approach.Most of all,this experiment suggests mediators from the CREB pathway as potential therapeutic targets on which we may influence to alter the wound healing dynamic of the cornea.We believe this study will lead to significant advancements in the clinical field of corneal defects.

Mesenchymal stem cells: Potential role in corneal wound repair and transplantation

Corneal diseases are a major cause of blindness in the world. Although great progress has been achieved in the treatment of corneal diseases, wound healing after severe corneal damage and immunosuppressive therapy after corneal transplantation remain prob-lematic. Mesenchymal stem cells(MSCs) derived from bone marrow or other adult tissues can differentiate into various types of mesenchymal lineages, such as osteocytes, adipocytes, and chondrocytes, both in vivo and in vitro. These cells can further differentiate into specific cell types under specific conditions. MSCs migrate to injury sites and promote wound healing by secreting anti-inflammatory and growth factors. In ad-dition, MSCs interact with innate and acquired immune cells and modulate the immune response through their powerful paracrine function. Over the last decade, MSCs have drawn considerable attention because of their beneficial properties and promising therapeutic prospective. Furthermore, MSCs have been applied to various studies related to wound healing, autoim-mune diseases, and organ transplantation. This review discusses the potential functions of MSCs in protecting corneal tissue and their possible mechanisms in corneal wound healing and corneal transplantation.

Comparison of cytotoxicity and wound healing effect of carboxymethylcellulose and hyaluronic acid on human corneal epithelial cells

AIM: To investigate the cytotoxic effect on human corneal epithelial cells(HCECs) and the ability to faciliate corneal epithelial wound healing of carboxymethylcellulose(CMC) and hyaluronic acid(HA).METHODS: HCECs were exposed to 0.5% CMC(Refresh plus, Allergan, Irvine, California, USA) and 0.1% and 0.3%HA(Kynex , Alcon, Seoul, Korea, and Hyalein mini,Santen, Osaka, Japan) for the period of 30 min, and 4, 12,and 24 h. Methyl thiazolyl tetrazoiun(MTT)-based calorimetric assay was performed to assess the metabolic activity of cellular proliferation and lactate dehydrogenase(LDH) leakage assay to assess the cytotoxicity. apoptotic response was evaluated with flow cytometric analysis and fluorescence staining with Annexin V and propiodium iodide. Cellular morphology was evaluated by inverted phase-contrast light microscopy and electron microscopy. The wound widths were measured 24 h after confluent HCECs were scratch wounded.RESULTS: The inhibitory effect of human corneal epithelial proliferation and cytotoxicity showed the time-dependent response but no significant effect. Apoptosis developed in flow cytometry and apoptotic cells weredemonstrated in fluorescent micrograph. The damaged HCECs were detached from the bottom of the dish and showed the well-developed vacuole formations. Both CMC and HA stimulated reepithehlialization of HCECs scratched, which were more observed in CMC.CONCLUSION: CMC and HA, used in artificial tear formulation, could be utilized without any significant toxic effect on HCECs. Both significantly stimulated HCEC reepithelialization of corneal wounds.

生物羊膜和角膜绷带镜对翼状胬肉手术后角膜创面修复的作用

背景:有文献报道,生物羊膜与角膜绷带镜应用于翼状胬肉术中均可明显减轻翼状胬肉切除术后疼痛反应、促进角膜创面愈合。目的:对比生物羊膜与角膜绷带镜对翼状胬肉术后角膜创面修复与神经性疼痛的影响。方法:选择南阳市第二人民医院2020年8月至2022年5月收治的原发性翼状胬肉患者121例(142眼),均接受翼状胬肉切除联合自体游离结膜瓣移植手术,其中63例(68眼)采用生物羊膜修复角膜创面(生物羊膜组),58例(74眼)采用硬性透氧性角膜接触镜修复角膜创面(绷带镜组)。术后随访,观察患者术后2周内的角膜创面修复情况;术后当天及术后1 d、2周,采用Wong-Baker脸评估神经性疼痛情况;术前、术后1个月、术后3个月,检测患者角膜地形图表面不对称指数、最佳矫正视力、角膜散光度及表面规则指数。结果与结论:①绷带镜组患者术后2周的角膜创面愈合率高于生物羊膜组(P<0.05),创面愈合时间短于生物羊膜组(P<0.01);②绷带镜组患者术后当天及术后1 d的神经性疼痛程度低于生物羊膜组(P<0.001),两组术后2周的神经性疼痛比较差异无显著性意义(P>0.05);③两组患者术后1,3个月的角膜地形图表面不对称指数、最佳矫正视力、角膜散光度及表面规则指数均较术前明显改善(P<0.05),绷带镜组患者术后1,3个月的角膜散光度、角膜地形图表面不对称指数及表面规则指数均低于生物羊膜组(P<0.05);④术后3个月内,生物羊膜组复发1眼(1.47%),绷带镜组复发3眼(4.05%),组间比较差异无显著性意义(P>0.05);⑤结果表明,与生物羊膜相比,角膜绷带镜修复翼状胬肉手术后角膜创面的效果更佳。

Tranilast inhibits TGF-β-induced collagen gel contraction mediated by human corneal fibroblasts

AIM： To determine if tranilast affects human corneal fibroblast（HCFs） contraction.METHODS： HCFs cultured in a three-dimensional type I collagen gel were treated with or without transforming growth factor beta（TGF-β） or tranilast. Gel diameter was measured as an indicator for collagen contraction. Immunoblot was performed to evaluate myosin light chain（MLC） and paxillin phosphorylation. Confocal microscopy was employed to examine the focal adhesions and actin stress fiber formation. Immunoblot analysis and gelatin zymography were performed to detect tissue inhibitors of metalloproteinases and matrix metalloproteinases（MMPs） in supernatant.RESULTS： The inhibitory effect of tranilast on HCFsmediated collagen gel contraction induced by TGF-β was dose-dependent. The significant effect of tranilast was started from 100 μmol/L and maximized at 300 μmol/L. The peak effect of 300 μmol/L tranilast also relied on the duration of treatment, which showed statistical significance from day 2. TGF-β-induced paxillin and MLC phosphorylation, stress fiber formation, focal adhesions, and MMP-1, MMP-2, and MMP-3 secretion in HCFs were also inhibited by tranilast.CONCLUSION： Tranilast suppresses the HCFs-cultured collagen gel contraction induced by TGF-β. It attenuates actin stress fibers formation, focal adhesions, and the secretion of MMPs, with these actions likely contributing to the inhibitory effect on HCF contractility. By attenuating the contractility of corneal fibroblasts, tranilast treatment may inhibit corneal scarring.

红外激光致角膜损伤的修复机制研究

目的探讨3.74μm红外激光致角膜损伤的修复机制。方法取27只6~8周龄C57BL/6J小鼠作为研究对象,将小鼠随机分为正常组(3只)和实验组(24只)。正常组不做任何处理,实验组小鼠用3.74μm红外激光照射双眼,光斑直径2 mm,曝光时间0.8 s,辐照量23.2 J·cm^(-2)。激光照射损伤后3 h、6 h、12 h、1 d、3 d、7 d、14 d、21 d各取3只实验组小鼠,连同正常组小鼠角膜组织进行病理切片,采用免疫组织化学染色检测中性粒细胞弹性蛋白酶、CD68、CD163以及血栓调节蛋白阳性细胞情况,鉴定新生血管发生情况。结果正常组小鼠角膜基质中均未见中性粒细胞弹性蛋白酶、CD68、CD163以及血栓调节蛋白阳性细胞。实验组小鼠中性粒细胞弹性蛋白酶阳性细胞在激光照射后3 h出现于角膜组织损伤边缘,12 h迁移至损伤区,1 d时数量最多,之后逐渐减少,21 d仍有少量阳性细胞;CD68阳性细胞在激光照射后12 h出现于角膜组织损伤边缘,1 d时出现在损伤区,21 d时仍有少量阳性细胞;CD163阳性细胞在激光照射后7 d出现于角膜组织损伤边缘,14 d时出现在损伤区,21 d仍有少量阳性细胞;血栓调节蛋白阳性细胞在激光照射后14~21 d出现于角膜基质损伤区。结论3.74μm红外激光可致角膜全层损伤,大量炎症细胞自损伤边界或角膜缘向损伤区迁移并参与修复过程。早期以中性粒细胞和M1型巨噬细胞浸润为主,后期以M2型巨噬细胞参与为主,并伴有新生血管生成。

Limbal stem cells: Central concepts of corneal epithelial homeostasis

A strong cohort of evidence exists that supports the localisation of corneal stem cells at the limbus. The distinguishing characteristics of limbal cells as stem cells include slow cycling properties, high proliferative potential when required, clonogenicity, absence of differentiation marker expression coupled with positive expression of progenitor markers, multipotency, centripetal migration, requirement for a distinct niche environment and the ability of transplanted limbal cells to regenerate the entire corneal epithelium. The existence of limbal stem cells supports the prevailing theory of corneal homeostasis, known as the XYZ hypothesis where X represents proliferation and stratification of limbal basal cells, Y centripetal migration of basal cells and Z desquamation of superficial cells. To maintain the mass of cornea, the sum of X and Y must equal Z and very elegant cell tracking experiments provide strong evidence in support of this theory. However, several recent stud-ies have suggested the existence of oligopotent stem cells capable of corneal maintenance outside of the limbus. This review presents a summary of data which led to the current concepts of corneal epithelial homeostasis and discusses areas of controversy surrounding the existence of a secondary stem cell reservoir on the corneal

Morphometric study of endothelial wound-healing following penetrating keratoplasty

Twenty samples of endothelia removed from normal and post penetrating keratoplas-ty (0.5,1,2,3 months after penetrating keratoplasty) were observed by scanning electron mi-croscopy.The photographs of the endothelia in graft-host junction were analyzed by computer-assisted image analysis system,and the morphometric indexes examined were area of the cells,perimeters,density,figure coefficient,long axis,coefficient of variation of the area,and oth-ers.Results showed that the morphology and the density of the endothelial cells changed obvi-ously after operation and improved slowly but progressively with time although at 3 monthspostoperatively some differences still existed.By using the new techniques,the experiment con-firmed and enriched the theories on the corneal endothelial wound-healing,revealing some ofthe new characters of the endothelial wound-healing following penetrating keratoplasty.

Netrin-1 promotes epithelium repair in corneal injury

●AIM:To explore netrin-1 functions on corneal epithelium in vitro and in vivo.●METHODS:In vitro the human corneal epithelial(HCE)cells were treated with serum free DMEM-F12 basic media containing 0,50,100,200,300,500,800,and 1000 ng/mL of netrin-1,respectively.The cells viability was detected by cell counting kit-8(CCK-8).The wound-healing assay was applied to assess the migration proficiency of HCE cells.Flow cytometry was used to analyze the cell-cycle distribution and apoptosis.In vivo,normal c57(6 wk)mice were demarcated with a trephine in the middle of the cornea to produce a 3-mm circular wound.Mice corneas were inflicted no epithelium with a 3-mm wound displayed,but remained the limbal epithelium intact.A blunt scalpel blade was used to remove the corneal epithelian cells,followed by topical netrin-1 application(200 ng/mL),and the group treated by PBS as control.The treated group was injected netrin-1 into the normal c57 mice inferior subconjunctival 4 h before trauma.Mouse corneal inflammation and neovascularization were observed under slit lamp microscope.The apoptosis of corneal cells was determined by TUNEL staining.●RESLUTS:A concentration of 200 ng/mL netrin-1 enhanced 25%of the HCE viability.The relative migration rates were 76.3%and 100%in control and netrin-1 treated group after cultured 72 h.Treated with netrin-1(200 ng/mL)decreased the apoptosis of HCE cells,as well as decreased their percentage from 19.3%±0.57%to 12.7%±0.42%of the total.The remaining wound area was 1.22 mm2 in control group but 0.22 mm2 in the netrin-1 treated group.Exogenous Netrin-1 inhibits apoptosis of corneal epithelial cells of c57 mice.TUNEL-positive cells at the epithelial layer of the corneas of the control and netrin-1 treated c57 mice at 24 h after wounding were 43.3%and 16.7%respectively.●CONCLUSION:Netrin-1 can reduce HCE apoptosis as well as promote its proliferation and migration.Topical application of netrin-1 promotes the injuryed cornea epithelial wound repair and inhibits apoptosis of corneal epithelial cells.These findings may offer potential therapies to repair the defects of corneal epithelial based on netrin-1.

角膜基质修复的机制和调控因素研究进展

角膜基质是维持角膜透明度的重要结构。外伤、感染、手术等可造成角膜基质损伤,引起修复的过程包括基质细胞表型改变、细胞外基质重塑、免疫细胞迁移。当基质严重受损,肌成纤维细胞增多和细胞外基质沉积发生基质纤维化反应,形成角膜瘢痕,是全球致盲的主要原因。目前治疗方式主要是角膜移植手术,因角膜供体资源短缺、手术技巧要求和术后移植排斥风险等治疗效果不佳。近年来,各种分子、细胞和组织对角膜基质损伤修复的调控机制取得一定研究进展。本文就角膜基质损伤修复的机制和角膜损伤原因、角膜结构、分子因素对角膜基质损伤修复的调控进行综述,为探索促进角膜基质修复和再生的途径提供新思路,希望帮助临床预防角膜瘢痕的发生。

溶血磷脂酸在眼部疾病作用中的研究进展

溶血磷脂酸(lysophosphatidic acid,LPA)是一种具有生物活性的天然甘油磷脂,它特异性地通过LPA受体与G蛋白耦连结合,通过多种途径参与细胞应激、信号传导、炎症反应、细胞保护等多种病理生理活动。LPA在眼部组织细胞中普遍存在并具有多种生理效应,如通过刺激角膜内皮细胞增殖促进角膜伤口愈合;诱导细胞外基质纤维化加重青光眼进展;通过晶状体上皮细胞增加游离钙浓度加重白内障的发展。此外,它在视网膜脱离和增殖性糖尿病视网膜病变的发生发展过程中也起着重要的作用。本文对LPA及其受体在眼部疾病作用中的研究进展给予综述。

角膜神经调控眼表微环境的研究进展

角膜是眼前段透明的外层结构,由高密度的神经组织支配。在角膜神经支配过程中,三叉神经节起源的角膜神经穿过上皮层和基质层中不同类型的角膜细胞。角膜基质细胞、上皮细胞、免疫细胞等多种细胞和角膜神经之间发生密切的相互作用,共同维持角膜微环境稳态。此外,角膜神经参与许多眼表疾病的发生发展过程。角膜神经释放多种活性肽物质,参与调控角膜感觉、维持上皮完整性和增殖、促进伤口愈合及调控角膜局部炎症和免疫反应等。本文对角膜神经在眼表微环境调控作用的研究进展进行综述,为角膜神经相关疾病的研究及治疗提供新的思路。

碱性成纤维细胞生长因子胶原罩对兔角膜穿透伤的影响

目的 :尝试一种新的用药方式———应用浸泡有碱性成纤维细胞生长因子 (bFGF)的胶原罩治疗兔角膜穿透伤。方法 :实验兔 30只 ,随机分为 3组 ,每组 10只 ,在角膜中心各作一穿透性长 4mm切口。第 1组 :对照组 ;第 2组 :2 μg/mL的bFGF溶液滴眼组 ;第 3组 :bFGF胶原罩治疗组。结果 :测得各组角膜伤口承受压力的极限值有明显差异 (P <0 0 0 0 5 ) ,对照组为 (62 0 0± 8 2 5 )kPa ;bFGF滴眼组为 (10 2 0 0± 13 4 3)kPa ;bFGF胶原罩组为 (135 83± 9 85 )kPa。 3组外伤的修复 :bFGF胶原罩组效果最好 ,bFGF滴眼组次之 ,对照组最差。结论 :3组角膜伤口均为疤痕修复 ,以bFGF胶原罩组最好。

表皮生长因子治疗兔角膜碱烧伤研究

本试验制成兔角膜碱烧伤模型，应用重组表皮生长因子（ｒｈＥＧＦ）滴眼剂对碱烧伤后的兔角膜溃疡创面进行治疗。６３只纯种新西兰白兔分为７组，每组９只，其中５组为治疗组，另２组为对照组，治疗组分别用每毫升０．５，５，２０，５０和１００μｇ表皮生长因子滴眼剂滴眼，对照组分别用纤维结合蛋白和氯霉素滴眼。伤后２４，４８，７２，９６及１２０ｈ裂隙灯荧光素染色，照像观察溃疡面积，经计算机图像处理，计算。结果显示５组治疗组创面愈合时间明显短于对照组，（Ｐ＜０．０５）。提示ＥＧＦ对角膜碱烧伤后的溃疡面愈合有促进作用。

重组人角质细胞生长因子-2对兔碱烧伤模型角膜上皮损伤的治疗作用

目的:研究外用旋滴重组人角质细胞生长因子-2(KGF-2)对兔碱烧伤模型角膜上皮损伤的治疗作用,为角膜上皮损伤的早期治疗探索新方法。方法:制备兔角膜碱烧伤模型,60只日本大耳白兔随机分为碱烧伤对照组和KGF-2组(25mg·mL-1)(n=30);各组日本大耳白兔于造模后以50μL药物滴眼,每日3次。7和14d裂隙灯观察角膜烧伤面积以及角膜新生血管的形成,MTT法检测角膜上皮细胞活性,免疫组化方法进行病理组织学检查。结果:碱烧伤后7和14d,KGF-2组角膜烧伤面积小于碱烧伤对照组,差异有显著性(P<0.01)。碱烧伤对照组7d角膜新生血管发生率为17.50%,KGF-2组为7.32%;碱烧伤对照组14d角膜新生血管发生率为41.67%,KGF-2组为32.50%。MTT检测结果显示:碱烧伤后7和14d,KGF-2组492nm吸光度与碱烧伤对照组比较差异有显著性(P<0.05或P<0.01)。碱烧伤后7和14d,病理切片HE染色显示:对照组角膜基质水肿,板层纤维排列松散、紊乱,炎症反应反复出现,角膜上皮层变薄,部分脱落,角膜内皮层内侧有大量成纤维细胞增生;KGF-2组碱烧伤后7d,角膜上皮细胞生长良好,基质轻度增厚,无明显的炎症反应;碱烧伤后14d,未出现炎症复发,角膜上皮细胞生长良好,排列整齐,角膜基质仅有轻度增厚。结论:外用旋滴25mg·mL-1KGF-2可加速角膜上皮损伤的恢复,减轻角膜烧伤的各种炎症反应症状;减轻角膜基质水肿和纤维化,同时KGF-2亦表现出显著的抑制角膜新生血管形成的作用;KGF-2有可能成为另一个对角膜上皮损伤具有重要调控作用的生长因子。

PRK后兔角膜成纤维细胞分泌产生bFGF、TGF-β_1及其对成纤维细胞增殖的影响

目的 探讨在准分子激光屈光手术后角膜伤口愈合过程中 ,是否有生长因子b FGF及 TGF- β1 参与 ,两种生长因子对成纤维细胞增殖的作用及其相应抗体对这一过程的影响。方法 对 PRK后兔角膜成纤维细胞原代培养 ,观察有否内源性生长因子 b FGF及 TGF-β1 的作用 ,内源性及外源性生长因子 b FGF及 TGF-β1 对细胞增殖的影响及相应抗体对抗原的中和作用。结果 在 PRK后兔角膜伤口愈合过程中成纤维细胞分泌产生b FGF及 TGF- β1 ,并刺激细胞的增殖 ,相应抗体可阻断这一生物效应。结论 (1)准分子激光屈光手术后角膜愈合过程中成纤维细胞分泌产生生长因子 b FGF及 TGF- β1 ;(2 )两种生长因子对角膜成纤维细胞的增殖具有刺激作用 ;(3)相应抗体可阻断 b FGF及 TGF- β1 对细胞增殖的刺激作用。本研究结果提示抗 b FGF抗体及抗 TGF- β1 抗体作为准分子激光屈光手术后选择性用药的可能性 ,可防止或减少屈光回退和角膜上皮下混浊等两个主要并发症 。

玻璃酸钠和重组牛bFGF滴眼液在角膜铁锈异物取出术后的疗效

目的:观察比较玻璃酸钠滴眼液和重组牛碱性成纤维细胞生长因子滴眼液联合应用对角膜铁锈异物取出术后角膜创面上皮修复的临床效果。方法:选择角膜铁锈异物患者98例98眼,随机分成联合治疗组49例49眼和对照组49例49眼。联合治疗组于角膜异物取出术后滴玻璃酸钠滴眼液+重组牛碱性成纤维细胞生长因子滴眼液+盐酸左氧氟沙星滴眼液;对照组滴重组牛碱性成纤维细胞生长因子滴眼液+盐酸左氧氟沙星滴眼液。每周3次观察角膜荧光素染色、角膜创面上皮修复及患眼局部症状等指标,观察2wk。结果:联合治疗组的总有效率96%高于对照组的88%(P<0.05)。结论:玻璃酸钠滴眼液和重组牛碱性成纤维细胞生长因子滴眼液联合应用能明显促进角膜损伤后上皮修复速度,疗效确切,安全可靠。

不同术式治疗翼状胬肉术后角膜修复情况的对比

目的:比较不同手术方法治疗原发性翼状胬肉术后角膜修复情况及术后不适症状的差异。方法:选取原发性翼状胬肉患者47例60眼分为两组,A组24例30眼,B组23例30眼。A组应用2.5mm巩膜隧道刀锐性切除角膜上翼状胬肉头部,B组应用有齿镊钝性分离撕除角膜上翼状胬肉头部。分别在术后1、3d,1wk,1mo观察角膜上皮修复情况及不适症状。结果:术后1、3d,B组的角膜修复优于A组。术后1d睁眼疼痛、畏光流泪、异物感A组较B组严重,差异具有统计学意义(P=0.005、0.015、0.012);术后3d睁眼疼痛、畏光流泪、异物感A组较B组严重,差异具有统计学意义(P=0.019、0.018、0.015);术后1wk,1mo不适症状两组无统计学差异(P>0.05)。结论:与锐性分离相比较,翼状胬肉手术最好选用钝性分离胬肉头部与角膜粘连。

角膜穿通伤后炎症因子的表达特征及其在房水中相对含量的动态变化

目的研究角膜穿通伤后炎症因子在眼球壁的分布特征及其在房水中相对含量的动态变化,初步探讨角膜穿通伤后眼内炎的发病机制。方法清洁级成年雌性SD(Sprague Dawley)大鼠50只,随机分为正常对照组和角膜穿通伤后6h、24h、48h、72h组,每组各10只。角膜穿通伤组大鼠制作角膜穿通伤模型,分别用免疫荧光染色法检测损伤后各时间点眼球壁组织中热休克蛋白90(heat shock protein90,HSP90)、肿瘤坏死因子-α(tumor necrosis factorα,TNF-α)、白细胞介素(interleukin,IL)-1β、IL-10的组织定位;并用免疫印迹法分别检测损伤后各时间点房水中上述因子相对含量的动态变化。结果 HSP90、IL-10、TNF-α和IL-1β在正常房水和眼球组织中含量较少。HSP90于损伤后6h在房水中含量达到高峰,与其他各组相比差异均有统计学意义(均为P<0.05),随后逐渐减少,免疫荧光染色结果显示其主要表达于视网膜视锥和视杆细胞层;TNF-α、IL-1β于损伤后24h在房水中达到高峰,与其他各组相比差异均有统计学意义(均为P<0.05),之后逐渐减少,主要表达于角膜、睫状体、视网膜;IL-10于损伤后72h在房水中含量达到高峰,与其他各组相比差异均有统计学意义(均为P<0.05),主要表达于角膜和视网膜。结论角膜穿通伤后应激反应可促使眼球局部炎症因子的表达,导致继发性炎症损伤。角膜穿通伤后应早期局部使用免疫抑制剂抑制炎症反应,保护眼球壁组织细胞。