新型生物组织工程角膜偏中心深板层移植治疗猫角膜损伤的临床研究

doi:10.11843/j.issn.0366-6964.2025.07.044

畜牧兽医学报 ›› 2025, Vol. 56 ›› Issue (7): 3528-3539.doi: 10.11843/j.issn.0366-6964.2025.07.044

新型生物组织工程角膜偏中心深板层移植治疗猫角膜损伤的临床研究

胥辉豪¹^,²^,*(), 李启卷¹, 邓航¹, 杜昕悦¹, 彭韵颖¹, 杨恒¹, 张德志¹, 曹礼静³, 甘玲¹, 郑小波¹, 易华山¹^,*()

1. 西南大学动物医学院，重庆 402460
2. 西南大学发光分析与分子传感教育部重点实验室，重庆 400700
3. 重庆市荣昌区职业教育中心，重庆 402460

收稿日期:2024-08-12 出版日期:2025-07-23 发布日期:2025-07-25
通讯作者: 胥辉豪,易华山 E-mail:xuhuihao2dai@163.com;dyxyihuashan@swu.edu.cn
作者简介:胥辉豪(1983-), 男, 重庆人, 副教授, 博士, 主要从事临床兽医学研究, E-mail: xuhuihao2dai@163.com, Tel: 023-68251603
基金资助:
国家万人计划教学名师工作室学员专项能力提升计划(4412200999)；重庆市现代农业产业技术体系资助(CQMAITS202312)；2023年西南大学教育教学改革专项(7140100026)；重庆市自然科学面上项目(2022NSCQ-MSX0419)；中央高校基本科研业务费专项资金(SWU-KT22015)；西南大学实验技术研究项目(SYJ2020013)；深圳市瑞鹏公益基金会高校青年教师(小动物临床)科研基金(RPJJ2020001)

Clinical Study of Novel Acellular Bioengineering Cornea Eccentric Deep Lamellar Keratoplasty for the Treatment of Feline Corneal Injury

XU Huihao¹^,²^,*(), LI Qijuan¹, DENG Hang¹, DU Xinyue¹, PENG Yunying¹, YANG Heng¹, ZHANG Dezhi¹, CAO Lijing³, GAN Ling¹, ZHENG Xiaobo¹, YI Huashan¹^,*()

1. College of Veterinary Medicine, Southwest University, Chongqing 402460, China
2. Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, Chongqing 400700, China
3. Chongqing Rongchang Vocatiaonal Education Center, Chongqing 402460, China

Received:2024-08-12 Online:2025-07-23 Published:2025-07-25
Contact: XU Huihao, YI Huashan E-mail:xuhuihao2dai@163.com;dyxyihuashan@swu.edu.cn

摘要/Abstract

摘要：

本研究旨在探究新型生物组织工程角膜——脱细胞生物工程角膜(acellular bioengineering cornea，ABC)偏中心深板层移植对猫角膜深层损伤的临床治疗效果及其愈合过程中相关细胞因子的调控机制。对36只成年健康本地猫建立角膜偏中心碱烧伤模型并随机平均分为3组：ABC移植组(ABCTs组)、角巩膜缘结膜瓣遮盖术组(CLCTs组)和模型组。通过裂隙灯检查、眼内压和泪液量的测量、角膜混浊度和荧光素染色评分、光学相干断层扫描(optical coherence tomography，OCT)以及组织病理学评价ABC偏中心深板层移植的临床效果和作用。结果显示：ABCTs组角膜透明度在各时间点均优于其他组，且角膜混浊度评分差异极显著(P＜0.01)。术后3组试验猫眼内压及泪液量均在正常生理范围内且荧光素染色评分总体均呈下降趋势，但ABCTs组角膜再上皮化时间显著早于其他组(P＜0.01)。OCT检查表明ABCTs组中移植物较CLCTs组更早地与宿主角膜基质融合，ABCTs组术后90 d时角膜厚度与正常角膜无显著性差异(P＞0.05)，而CLCTs组角膜厚度极显著降低(P＜0.01)。组织学观察发现ABCTs组角膜组织中炎性细胞相比于CLCTs组较少，角膜胶原排列更规则。综上，ABC移植可有效治疗猫偏中心角膜损伤并提供卓越的角膜透光度，ABC可能通过减少胶原纤维和瘢痕的生成，促进角膜的修复和透明度的恢复。

关键词: 猫, 新型脱细胞生物工程角膜, 角膜偏中心损伤, 深板层角膜移植术

Abstract:

The purpose of this study is to investigate the clinical therapeutic effect of a novel acellular bioengineering cornea (ABC) with eccentric lamellar keratoplasty on deep corneal injury in cats and the regulatory mechanism of related cytokines during the healing process. A corneal eccentric alkali burn model in 36 healthy adult local cats was established, and the model animals were randomly divided into three groups: ABC transplantation group (ABCTs group), corneal limbal conjunctival transplant group (CLCTs group), and control group. Evaluate the clinical efficacy and role of ABC eccentric deep lamellar keratoplasty through slit lamp examination, measurement of intraocular pressure and tear volume, corneal opacity and fluorescein staining score, optical coherence tomography (OCT) and histopathology. The corneal transparency of the ABCTs group was superior to other groups at all time-points, and the difference in corneal opacity score was extremely significant (P < 0.01). The intraocular pressure and tear volume of the three groups after surgery were within the normal physiological range, and the fluorescein staining scores showed an overall decreasing trend. However, the corneal re-epithelialization time in the ABCTs group was significantly earlier than that in the other groups (P < 0.01). OCT examination showed that the ABCTs group had earlier fusion of the graft with the host corneal stroma compared to the CLCTs group. There was no significant difference in corneal thickness between the ABCTs group and the normal cornea at 90 days after surgery (P>0.05), while the CLCTs group showed a significant decrease in corneal thickness (P < 0.01). Histological observation revealed that the ABCTs group had fewer inflammatory cells in corneal tissue compared to the CLCTs group, and the arrangement of corneal collagen was more regular. ABC transplantation can effectively treat cat eccentric corneal injury and provide excellent corneal transparency. ABC may promote corneal repair and transparency recovery by reducing collagen fibers and formation of scars.

Key words: feline, novel acellular bioengineering cornea, eccentric corneal injury, deep lamellar keratoplasty

中图分类号:

S857.6

胥辉豪, 李启卷, 邓航, 杜昕悦, 彭韵颖, 杨恒, 张德志, 曹礼静, 甘玲, 郑小波, 易华山. 新型生物组织工程角膜偏中心深板层移植治疗猫角膜损伤的临床研究[J]. 畜牧兽医学报, 2025, 56(7): 3528-3539.

XU Huihao, LI Qijuan, DENG Hang, DU Xinyue, PENG Yunying, YANG Heng, ZHANG Dezhi, CAO Lijing, GAN Ling, ZHENG Xiaobo, YI Huashan. Clinical Study of Novel Acellular Bioengineering Cornea Eccentric Deep Lamellar Keratoplasty for the Treatment of Feline Corneal Injury[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(7): 3528-3539.

图/表 15

图 1

图 2

图 3

图 4

图 5

图 6

图 7

图 8

图 9

图 10

图 11

图 12

图 13

图 14

图 15

参考文献 28

1	王洪斌. 家畜外科学[M]. 北京: 中国农业出版社, 2002.
	WANG H B . Animal surgery[M]. Beijing: China Agriculture Press, 2022.
2	DELMONTE D W , KIM T . Anatomy and physiology of the Cornea[J]. J Cataract Refract Surg, 2011, 37 (3): 588- 598.
3	刘景晨, 李明军, 孙曙光, 等. 眼科领域应用的脱细胞组织材料[J]. 中国组织工程研究, 2021, 25 (34): 5530- 5536.
	LIU J C , LI M J , SUN S G , et al. Application of acellular tissue in ophthalmology[J]. Chinese Journal of Tissue Engineering Research, 2021, 25 (34): 5530- 5536.
4	胥辉豪, 金艺鹏, 张迪, 等. 改良角膜结膜移植术治疗猫坏死性角膜炎病例[J]. 中国兽医杂志, 2019, 55 (8): 68-70, 136.
	XU H H , JIN Y P , ZHANG D , et al. Improved corneal conjunctival transplantation for the treatment of sequestrum in cats[J]. Chinese Journal of Veterinary Medicine, 2019, 55 (8): 68-70, 136.
5	BELKNAP E B . Corneal emergencies[J]. Top Companion Ani Med, 2015, 30 (3): 74- 80.
6	TETAS PONT R , MATAS RIERA M , NEWTON R , et al. Corneal and anterior segment foreign body trauma in dogs: A review of 218 cases[J]. Vet Ophthalmol, 2016, 19 (5): 386- 397.
7	WILLIAMS D L , KIM J Y . Feline entropion: A case series of 50 affected animals (2002008)[J]. Vet Ophthalmol, 2009, 12 (4): 221- 226.
8	MANDELL D C . Ophthalmic emergencies[J]. Clin Tech Small Ani Pract, 2000, 15 (2): 94- 100.
9	XU H , SAPIENZA J S , JIN Y , et al. Lamellar keratoplasty using acellular bioengineering cornea (BioCorneaVet^TM) for the treatment of feline corneal sequestrum: A retrospective study of 62 eyes (2018-2021)[J]. Animals (Basel), 2022, 12 (8): 1016.
10	DANG D H , RIAZ K M , KARAMICHOS D . Treatment of non-infectious corneal injury: Review of diagnostic agents, therapeutic medications, and future targets[J]. Drugs, 2022, 82 (2): 145- 167.
11	LJUBIMOV A V , SAGHIZADEH M . Progress in corneal wound healing[J]. Prog Retinal Eye Res, 2015, 49, 17- 45.
12	戴馨萱. 板层角膜移植术治疗角膜病变的临床疗效分析[D]. 长春: 吉林大学, 2022.
	DAI X X. Clinical effect analysis of lamellar keratoplasty for keratopathy[D]. Changchun: Jilin University, 2021. (in Chinese)
13	WANG Q , ZHOU H , SUN Y , et al. Modified acellular porcine corneal matrix in deep lamellar transplantation of rabbit cornea[J]. J Biomater Appl, 2020, 34 (8): 1092- 1104.
14	程燕, 刘先宁, 吴洁, 等. 复方倍他米松对异种角膜板层移植术后免疫排斥反应的影响[J]. 国际眼科杂志, 2018, 18 (1): 21- 26.
	CHENG Y , LIU X N , WU J , et al. Effect of compound betamethasone on immunological rejection after xenogeneic corneal lamellar transplantation[J]. International Eye Science, 2018, 18 (1): 21- 26.
15	PFISTER R R , HADDOX J L , YUILLE-BARR D . The combined effect of citrate/ascorbate treatment in alkali-injured rabbit eyes[J]. Cornea, 1991, 10 (2): 100- 104.
16	HEILIGENHAUS A , BERRA A , FOSTER C S . CD4+V beta 8+ T cells mediate herpes stromal keratitis[J]. Curr Eye Res, 1994, 13 (10): 711- 716.
17	SPIESS B M , POT S A , FLORIN M , et al. Corneal collagen cross-linking (CXL) for the treatment of melting keratitis in cats and dogs: A pilot study[J]. Vet Ophthalmol, 2014, 17 (1): 1- 11.
18	CHEN Y M , HU F R , HUANG J Y , et al. The effect of topical autologous serum on graft re-epithelialization after penetrating keratoplasty[J]. Am J Ophthalmol, 2010, 150 (3): 352- 359.
19	SANTILLO D , MATHIESON I , CORSI F , et al. The use of acellular porcine corneal stroma xenograft (BioCorneaVet^TM) for the treatment of deep stromal and full thickness corneal defects: A retrospective study of 40 cases (2019-2021)[J]. Vet Ophthalmol, 2021, 24 (5): 469- 483.
20	SHAFIQ M A , GEMEINHART R A , YUE B Y , et al. Decellularized human cornea for reconstructing the corneal epithelium and anterior stroma[J]. Tissue Eng Part C Methods, 2012, 18 (5): 340- 348.
21	胥辉豪, 郑小波, 金艺鹏, 等. 生物组织工程角膜穿透性移植治疗猫角膜坏死性穿孔[J]. 中国兽医杂志, 2021, 57 (11): 101- 104.
	XU H H , ZHENG X B , JIN Y P , et al. Biological tissue engineering corneal penetrating transplantation for the treatment of sequestrum perforation in a cat[J]. Chinese Journal of Veterinary Medicine, 2021, 57 (11): 101- 104.
22	唐静. 不同滴眼液对犬穿透性人工角膜移植术术后抗免疫排斥反应的研究[D]. 重庆: 西南大学, 2022.
	TANG J. Research of different eyedrops on anti-immunity rejection after penetrating keratoplasty in canine[D]. Chongqing: Southwest University, 2022. (in Chinese)
23	ROSOLEN S G , RIVIÈRE M-L K , LAVILLEGRAND S , et al. Use of a combined slit-lamp SD-OCT to obtain anterior and posterior segment images in selected animal species[J]. Vet Ophthalmol, 2012, 15 (Suppl 2): 105- 115.
24	ISIDAN A , LIU S , LI P , et al. Decellularization methods for developing porcine corneal xenografts and future perspectives[J]. Xenotransplantation, 2019, 26 (6): e12564.
25	张丽霞. 长链非编码RNA LINC00963抑制角膜纤维化瘢痕形成的机制研究[D]. 青岛: 青岛大学, 2021.
	ZHANG L X. The long noncoding RNA LINC00963 inhibits corneal fibrosis scar formation by targeting miR-143-3p[D]. Qingdao: Qingdao University, 2021. (in Chinese)
26	GHOSH T , MAITY N , SUR V P , et al. Mitigating fibrosis-an impediment to corneal re-innervation following lamellar flap surgery[J]. Exp Eye Res, 2020, 194, 108009.
27	HUH M I , KIM Y H , PARK J H , et al. Distribution of TGF-beta isoforms and signaling intermediates in corneal fibrotic wound repair[J]. J Cell Biochem, 2009, 108 (2): 476- 488.
28	YI Q , ZOU W J . The wound healing effect of doxycycline after corneal alkali burn in rats[J]. J Ophthalmol, 2019, 2019, 5168652.

[1]	郑艺蕾, 沈冯婷, 辛良, 袁希望, 林琳, 曹迪, 吴旧生, 师福山, 王华南. 一例猫鼻神经内分泌恶性肿瘤的病理和免疫组化分析[J]. 畜牧兽医学报, 2025, 56(6): 2948-2956.
[2]	姜林, 张耀辉, 黎静, 张晓晶. 影像学技术在犬猫常见心脏疾病诊断中的应用[J]. 畜牧兽医学报, 2025, 56(5): 2103-2111.
[3]	朱秋祥, 胡雨林, 朱鑫超, 钟永澄, 丁晓晴, 冀锦朝, 王京煜, 贾坤, 张海洋, 李守军. 猫急性应激诊断标准的完善及其在加巴喷丁片临床试验中的应用[J]. 畜牧兽医学报, 2025, 56(5): 2424-2437.
[4]	卢娜, 高钰, 赵嘉伟, 苏迪, 陈家磊, 罗忠礼. 猫传染性腹膜炎病毒mRNA疫苗转录载体的构建与鉴定[J]. 畜牧兽医学报, 2025, 56(2): 803-813.
[5]	郑焕琴, 姜晓敏, 岳红, 王宝岩, 刘洋, 张兴晓, 张建龙, 朱洪伟. 猫1型疱疹病毒分离鉴定及部分生物学特性分析[J]. 畜牧兽医学报, 2024, 55(7): 3040-3048.
[6]	孙凡媛, 刘怡婷, 郭昕怡, 陈建材, 周华波, 覃一峰, 欧阳康, 韦祖樟, 黄伟坚, 陈樱. 猫上呼吸道疾病的病原、诊断与防治[J]. 畜牧兽医学报, 2024, 55(6): 2345-2356.
[7]	周宁, 汤承, 许佳, 岳华, 陈曦. 猫泛白细胞减少症病毒A91S变异株对猫的致病性及基因组特征研究[J]. 畜牧兽医学报, 2024, 55(6): 2560-2568.
[8]	李春晓, 安尉, 高博泉, 王振龙, 韩冰, 陶慧, 王金全, 王秀敏. 猫犬主要过敏原蛋白的最新研究进展[J]. 畜牧兽医学报, 2024, 55(2): 471-480.
[9]	张泽宇, 董宁宁, 谈晓梅, 李传锋, 朱杰, 刘光清, 张伟, 孟春春. 猫杯状病毒VP1蛋白的单克隆抗体制备及抗原表位鉴定[J]. 畜牧兽医学报, 2024, 55(12): 5784-5791.
[10]	康博, 郭瑞泽, 张迪. 计算机断层扫描淋巴管造影技术在猫乳糜胸诊疗中的应用[J]. 畜牧兽医学报, 2024, 55(11): 4890-4899.
[11]	刘福康, 袁莉刚, 张达, 汤傲星, 刘光清, 朱杰. 猫传染性腹膜炎病毒N蛋白表达及其多克隆抗体制备[J]. 畜牧兽医学报, 2024, 55(10): 4773-4778.
[12]	范小雨, 米洁, 刘佳琦, 菅玉双, 李四豪, 范云鹏, 刘迎秋, 宋晓平, 张为民, 麻武仁. 回阳九针术对母猫绝育术后苏醒监测指标的影响[J]. 畜牧兽医学报, 2024, 55(1): 365-372.
[13]	王莹, 李佳康, 曾悦, 史开拓, 韦丽婷, 彭佳佳, 李秋燕, 曹龙龙, 周登元. 猫杯状病毒单克隆抗体的制备[J]. 畜牧兽医学报, 2024, 55(1): 401-405.
[14]	眭玉珍, 陈桂珍, 左守军, 汪海东, 宋鹏涛, 栗亮亮, 张龙现, 董海聚, 刘芳. 河南省宠物猫华支睾吸虫和其他肠道寄生虫感染状况分析[J]. 畜牧兽医学报, 2023, 54(7): 3022-3030.
[15]	胥辉豪, 冯雪倩, 朴雪玲, 慎晓军, 郑小波, 杨恒, 林珈好, 金艺鹏, 林德贵. 猫角膜缘干细胞不同采集、分离与培养鉴定方法的对比研究[J]. 畜牧兽医学报, 2023, 54(7): 3091-3101.

新型生物组织工程角膜偏中心深板层移植治疗猫角膜损伤的临床研究

Clinical Study of Novel Acellular Bioengineering Cornea Eccentric Deep Lamellar Keratoplasty for the Treatment of Feline Corneal Injury

PDF

可视化

摘要/Abstract

引用本文

使用本文

图/表 15

参考文献 28

相关文章 15

编辑推荐

Metrics

本文评价