Validation of glaucoma-like features in the rat episcleral vein cauterization model.
BACKGROUND
Glaucoma, an irreversible optic nerve neuropathy, always results in blindness. This study aimed to evaluate glaucoma-like features in the rat episcleral vein cauterization (EVC) model by multiple in vivo and in vitro evidences.


METHODS
Wistar rat was used in this study. The elevated intraocular pressure (IOP) was induced by cauterization of three episcleral veins. IOP was monitored with Tono-Pen XL tonometer. Time-dependent changes to the neuronal retinal layers were quantified by Fourier domain-optical coherence tomography. The function of retina was evaluated by electroretinogram (ERG). Survival of retinal ganglion cells (RGCs) was quantified by retrograde labeling. Histology study was performed with retinal sections stained with hematoxylin-eosin, glial fibrillary acidic protein, and neuronal nuclear antigen. Retina and aqueous humor protein were extracted and cytotoxic protein tumor necrosis factor alpha (TNF-α) and alpha-2 macroglobulin (α2m) were measured with Western blotting.


RESULTS
EVC is a relatively facile intervention, with low failure rates (<5%). After surgical intervention, chronic mild IOP elevation (about 1.6-fold over normal, P < 0.05) was induced for at least 6 weeks without requiring a second intervention. High IOP causes chronic and progressive loss of RGCs (averaging about 4% per week), progressive thinning of neuronal retinal layers (3-5 μm per week), and reduction of a- and b-wave in ERG. EVC method can also induce glial cell activation and alterations of inflammation proteins, such as TNF-α and α2m.


CONCLUSIONS
EVC method can establish a robust, reliable, economic and highly reproducible glaucomatous animal model.
Key Laboratory of Vision Loss and Restoration, Ministry of Education; Department of Ophthalmology, Peking University People's Hospital, Beijing 100044, China; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China.
Yujing
Y
Bai
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China.
Yingting
Y
Zhu
Department of Ophthalmology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Qin
Q
Chen
Engineering Science, Simon Fraser University, Burnaby, BC, Canada, V5A 1S6.
Jing
J
Xu
Engineering Science, Simon Fraser University, Burnaby, BC, Canada, V5A 1S6.
Marinko V
MV
Sarunic
Department of Pharmacology and Therapeutics, Department of Oncology and the Cancer Center, Bloomfield Centre for Research in Aging, Lady Davis Institute-Jewish General Hospital, McGill University, Montreal, Quebec, Canada H3T 1E2.
Uri H
UH
Saragovi
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China. Email: zhuoyh@mail.sysu.edu.cn.
Yehong
Y
Zhuo
D000818:Animals; D004195:Disease Models, Animal; D004596:Electroretinography; D005260:Female; D005901:Glaucoma / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000378:metabolism / Q000473:pathology; D055351:Retinal Neurons / Q000378:metabolism