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Abstract #25793 Published in IGR 12-2
Susceptibility of CYP1B1 knock-out mouse to glaucoma in a high glucocorticoid environment
Wu C; Jiang F-G; Liu X-WChinese Ophthalmic Research 2010; 28: 385-389
Background: Genetic factors involves the pathogenesis of primary congenital glaucoma (PCG). It has already been confirmed that CYP1B1 is located in GLC3A, one of the disease-causing genes on PCG-related loci. However, whether the occurrence of PCG is caused directly by the CYP1B1 mutations or with other genetic or environmental factor remains unclear. Objective: The present study was to investigate the susceptibility of glaucoma in CYP1B1 gene knock-out mouse under high dosage of glucocorticoid environment. Methods: Glaucoma models were induced by subconjunctival injection of 0.04 mL betamethasone for 4 times at 3-day interval in the right eyes of 40 SPF adult CYP1B1(-/-) mice. Forty SPF adult C57BL/6J mice with the same treatment method were as control. The intraocular pressure (IOP) of mice were measured by Tono-pen XL applanometer once a week before and after the injection. The animals were sacrificed, their eyeballs were enucleated, and retinal thickness were evaluated under the light microscope before and 4 weeks, 8 weeks, 12 weeks after injection respectively. The apoptosis of retinal ganglion cells (RGCs) was detected by terminal deoxnucleotidyl transferase mediated dUTP biotin nick end labeling (TUNEL). This experiment followed Guide to the Care and Use of Experimental Animals (NIH publication No. 23-85, revised 1996). Results: The IOP was persistently elevated in 4, 8 and 12 weeks after the injection of betamethasone in comparison with before injection in both CYP1B1(-/-) mice and C57BL/6J mice (P < 0.05), and the IOP of CYP1B1(-/-) mice was significantly higher than that of C57BL/6J mice in 8 and 12 weeks after the injection of betamethasone (P < 0.05). Retinal fibrous layer was gradually thinner with the prolong of time after injection of betamethasone in both CYP1B1(-/-) mice and C57BL/6J mice (P < 0.05). The thickness of retinal fibrous layer in CYP1B1 (-/-) mice was obviously thinner than that of C57BL/6J mice in 8 and 12 weeks after the injection of betamethasone (P < 0.05). Apoptosis rate of RGCs was increased after the injection of betamethasone compared with before the injection in both CYP1B1(-/-) mice and C57BL/6J mice (P < 0.05), especially in CYP1B1(-/-) mice (P < 0.05). Conclusion: In an environment of high level glucocorticoid, the susceptibility to glaucoma is increased higher in CYP1B1(-/-) mice. LA: Chinese
C. Wu. Department of Ophthalmology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Classification:
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
9.4.1 Steroid-induced glaucoma (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders)