北京生物医学工程

慢性高眼压作用下视网膜功能及筛板形态改变

Changes of retinal function and morphology of lamina cribrosa under chronic ocular hypertension

作者：张景茜任璐頔钱秀清

单位：首都医科大学生物医学工程学院（北京 100069）<br />首都医科大学临床生物力学应用基础研究北京市重点实验室（北京 100069）<br />通信作者：钱秀清。E-mail: qianxq@ccmu.edu.cn

分类号：R318.04

出版年·卷·期（页码）：2022·41·5（447-453）

摘要：

目的本研究通过视觉电生理测试技术和激光共聚焦图像获取技术研究慢性高眼压作用下视网膜功能及筛板形态的改变情况，为青光眼致病机制研究提供基础。方法通过建立慢性高眼压动物模型，对正常大鼠和造模后2周、4周大鼠进行闪光视网膜电图（flash electroretinogram，F-ERG）、闪光视觉诱发电位（flash visual evoked potential，F-VEP）测试，并通过共聚焦显微镜对筛板组织切片进行观察，计算孔隙率。结果慢性高眼压造模2周后，F-VEP的P1潜时下降、N2潜时显著增长；造模4周后，F-ERG中Rod-ERG、Cone-ERG的b 波幅值显著下降，Max-ERG的a波幅值和b波幅值均显著下降，Flick-ERG的峰值幅值显著下降，各反应波形的潜时没有明显变化，鼠眼筛板孔隙率升高。结论慢性高眼压作用2周后，视神经的轴突、髓鞘功能下降。高眼压作用4周后视网膜感光功能进一步衰减，同时筛板组织胶原排列发生变化，筛孔面积比例增加。

Objective This study aims to study the changes of retinal function and morphology of lamina cribrosa under chronic ocular hypertension by using visual electrophysiological test and confocal microscope test, and to provide a basis for the pathogenic mechanism research of glaucoma. Methods By inducing a rat model of chronic ocular hypertension, we performed flash electroretinogram (F-ERG) and flash visual evoked potential (F-VEP) tests on normal rats and two weeks, four weeks rats after modeling, and observed the lamina cribrosa tissue slices through a confocal microscope, and then calculated the porosity of lamina cribrosa. Results Two weeks after chronic ocular hypertension, the results of P1 latency of F-VEP decreased and the N2 latency increased significantly compared with the control group. Four weeks after chronic ocular hypertension, the b-wave amplitude of Rod-ERG and Cone-ERG in F-ERG decreased, and the a-wave amplitude and b-wave amplitude of Max-ERG decreased, and the peak amplitude of Flick-ERG decreased significantly. There was no obvious change in the latency of each response waveform. The porosity of lamina cribrosa increased. Conclusions The function of optic nerve axon and myelin sheath of rats degrade after two weeks of chronic ocular hypertension. Four weeks after chronic ocular hypertension, the photoreceptive function of the retina degrades. While the arrangement of lamina beam changes and the proportion of lamina pores increases.

参考文献：

[1] Tham YC, Li X, Wong TY, et al. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis [J]. Ophthalmology, 2014, 121(11): 2081-2090.
[2] Prencipe M, Perossini T, Brancoli G, et al. The photopic negative response (PhNR): measurement approaches and utility in glaucoma [J]. International Ophthalmology, 2020, 40(12): 3565-3576.
[3] Eastlake K, Jayaram H, Luis J, et al. Strain specific responses in a microbead rat model of experimental glaucoma [J]. Current Eye Research, 2021, 46(3): 387-397.
[4] John CM, Johnson E, William OC. Rat models for glaucoma research [J]. Progress in Brain Research, 2008, 173: 285-301.?
[5] 魏文, 李运, 杨晓冉, 等. 慢性高眼压致兔视神经及视功能的损伤[J]. 中国老年学杂志, 2012, 32(3): 525-528.
Wei W, Li Y, Yang XR, et al. The configuration and function of retinal damage during intraocular hypertension in rabbits[J]. Chinese Journal of Gerontology, 2012, 32(3): 525-528.
[6] Wu X, Pang Y, Zhang Z, et al. Mitochondria-targeted antioxidant peptide SS-31 mediates neuroprotection in a rat experimental glaucoma model [J]. Acta Biochimica et Biophysica Sinica (Shanghai), 2019, 51(4): 411-421.
[7] ElGohary AA, Elshazly LH. Photopic negative response in diagnosis of glaucoma: an experimental study in glaucomatous rabbit model [J]. International Journal of Ophthalmology, 2015, 8(3): 459-464.
[8] Porciatti V. Electrophysiological assessment of retinal ganglion cell function[J]. Experimental Eye Research, 2015, 141: 164-70.
[9] Whatham AR, Nguyen V, Zhu Y, et al. The value of clinical electrophysiology in the assessment of the eye and visual system in the era of advanced imaging [J]. Clinical and Experimental Optometry, 2014, 97(2): 99-115.
[10] 党文婕, 张旭. 视觉电生理检查在青光眼早期诊断中作用的研究进展[J]. 中华眼科杂志, 2018, 54(11): 868-872.
Dang WJ, Zhang X. Electrophysiology and early glaucoma diagnosis[J]. Chinese Journal of Ophthalmology, 2018, 54(11): 868-872.
[11] 王霞, 潘英姿. 视觉诱发电位在青光眼视功能检测方面的研究进展[J]. 中华眼科杂志, 2020, 56(1): 61-65.
Wang X, Pan YZ. Research progression of visual evoked potential in glaucomatous visual function evaluation[J]. Chinese Journal of Ophthalmology, 2020, 56(1): 61-65.
[12] 张婷, 李龙, 宋凡. 青光眼发病机理—筛板变形研究进展[J]. 力学学报, 2019, 51(05): 1273-1284.
Zhang T, Li L, Song F. Pathogenetic mechanisms of glaucoma-research process on the deformation of lamina cribrosa[J]. Chinese Journal of Theoretical and Applied Mechanics, 2019, 51(05): 1273-1284.
[13] Peng F, Ma LP, Liu L, et al. Preliminary study on the blockade of axonal transport by activated astrocytes in optic nerve head under chronic ocular hypertension[J]. Journal of Mechanics in Medicine and Biology, 2019, 19(7): 1940040.
[14] 马丽萍, 刘浏, 郭学谦, 刘志成, 钱秀清. 急性高眼压作用下视神经轴浆运输与视网膜光学功能的关系[J]. 中国医学物理学杂志, 2017, 34(10): 1035-1040.
Ma LP, Liu L, Guo XQ, et al. Relationship between the axonal transport of the optic nerve and the optical function of the retina in acute high intraocular pressure[J]. Chinese Journal of Medical Physics, 2017, 34(10): 1035-1040.
[15] Tezel G, Trinkaus K, Wax MB. Alterations in the morphology of lamina cribrosa pores in glaucomatous eyes[J]. British Journal of Ophthalmology, 2004, 88(2): 251-256.
[16] Voorhees AP, Jan NJ, Austin ME, et al. Lamina cribrosa pore shape and size as predictors of neural tissue mechanical insult[J]. Investigative Ophthalmology and Visual Science, 2017, 58(12): 5336-5346.
[17] Tan Li, Lin Li, Zhicheng Liu. Time course changes of the mechanical properties of the iris pigment epithelium in a rat chronic ocular hypertension model[J]. BioMed Research International, 2018, 2018: 4862309.
[18] Yu H, Zhong H, Chen J, et al. Efficacy, drug sensitivity, and safety of a chronic ocular hypertension rat model established using a single intracameral injection of hydrogel into the anterior chamber[J]. Medical Science Monitor, 2020, 26: e925852.
[19] Chen J, Sun J, Yu H, et al. Evaluation of the effectiveness of a chronic ocular hypertension mouse model induced by intracameral injection of cross-linking hydrogel[J]. Frontiers in Medicine (Lausanne), 2021, 8: 643402.
[20] 郭学谦, 田蓓, 孙世杰, 等. 高眼压对青光眼视网膜功能的影响[J]. 医用生物力学, 2010, 25(3): 195-199.
Guo XQ, Tian B, Sun SJ, et al. Effect of ocular hypertension on the function of retina of glaucoma[J]. Journal of Medical Biomechanics, 2010, 25(3): 195-199.
[21] Hannon BG, Feola AJ, Gerberich BG, Read AT, Prausnitz MR, Ethier CR, Pardue MT. Using retinal function to define ischemic exclusion criteria for animal models of glaucoma. Experimental Eye Research. 2021,202:108354.
[22] Cvenkel B, Sustar M, Perov?ek D. Ganglion cell loss in early glaucoma, as assessed by photopic negative response, pattern electroretinogram, and spectral-domain optical coherence tomography [J]. Documenta Ophthalmologica, 2017, 135(1): 17-28.
[23] Fortune B, Burgoyne CF, Cull GA, et al. Structural and functional abnormalities of retinal ganglion cells measured in vivo at the onset of optic nerve head surface change in experimental glaucoma[J]. Investigative Ophthalmology and Visual Science, 2012, 53(7): 3939-3950.
[24] Fortune B, Cull G, Reynaud J, et al. Relating retinal ganglion cell function and retinal nerve fiber layer (RNFL) retardance to progressive loss of RNFL thickness and optic nerve axons in experimental glaucoma[J]. Investigative Ophthalmology and Visual Science, 2015, 56(6): 3936-3944.
[25] Liu HH, Flanagan JG. A mouse model of chronic ocular hypertension induced by circumlimbal suture[J]. Investigative Ophthalmology and Visual Science, 2017, 58(1): 353-361.
[26] Tan B, MacLellan B, Mason E, et al. Structural, functional and blood perfusion changes in the rat retina associated with elevated intraocular pressure, measured simultaneously with a combined OCT+ERG system[J]. PLoS One, 2018, 13(3): e0193592.
[27] Tan B, Gurdita A, Choh V, et al. Morphological and functional changes in the rat retina associated with 2 months of intermittent moderate intraocular pressure elevation[J]. Scientific Reports, 2018, 8(1): 7727.

服务与反馈：

【文章下载】【加入收藏】

提示：您还未登录，请登录！点此登录