Abstract
Abstract: :
Purpose:To localize the expression of cyclooxygenase–2 (COX–2) in the retina and to investigate the effect of a COX–2 inhibitor, meloxicam, on the mouse model of retinopathy of prematurity (ROP). Methods: Seventy C57BL/6 mice of postnatal day (P) 7 were included in this study. To induce ROP, 40 mice were exposed to 75 +/– 5% oxygen from P7 to P12 and then placed in room air from P12 to P17. The COX–2 inhibitor, meloxicam (1mg/kg) was injected into 20 of them intraperitoneally from P13 to P17 (Group 1), and the same amount of normal saline was injected into the other 20 mice (Group 2). Thirty normal mice which were placed in room air from birth to P17, were considered as control. The same amount of meloxicam was injected to 15 of control mice (Group 3) and normal saline injection was done to the rest of the control mice (Group 4). All mice were sacrificed at P20. Immunohistochemistry for COX–2 was performed on retinas of all groups and Mayer hematoxylin and eosin stain was used to measure blood vessel profiles (BVPs) in the inner retina. Systemic perfusion was performed using high–molecular–weight (MW=2,000,000) fluorescein–conjugated dextran to examine the retinal vascular pattern. Change of body weight was compared among the groups to evaluate the possible side effect of meloxicam on the growth of the mouse. Results: In all groups, positive immunolabeling for COX–2 was observed in the cytoplasm of ganglion cells, retinal blood vessels, and outer plexiform layer. A lot of large vessels were observed in the inner retina and vitreous cavity, including the vessels adherent to inner limiting membrane in group 2. The BVPs of group 1 were significantly smaller than group 2 (by 34.8%, p = 0.005). The BVPs of group 3 were smaller than group 4 also (by 24.2%), but it was not statistically significant (p = 0.107). The ROP score in group 2 was significantly higher than in group 1 (p = 0.014), but there was no significant difference between group 3 and group 4 (p = 0.542). Change of body weight was not significantly different between meloxicam injection groups (groups 1 and 3) and non–injection groups (groups 2 and 4). Conclusions: We verified the expression of COX–2 in the retina and demonstrated the antiangiogenic effect of COX–2 inhibitor, meloxicam, on the mouse model of ROP. This property of COX–2 inhibitor can be used in the treatment of angiogenic retinal disease such as ROP and proliferative diabetic retinopathy, and it can be considered as a substitute for nonselective COX inhibitors and dexamethasone to avoid of potential side effects of these drugs.
Keywords: retinopathy of prematurity • retinal development • retinal neovascularization