Topical ocular dexamethasone decreases intraocular pressure and body weight in rats.
Topical ocular dexamethasone decreases intraocular pressure and body weight in rats.
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DOI：
10.1186/s12952-016-0048-x
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发表时间：
2016-03-12
期刊：
影响因子：
--
通讯作者：
Nakazawa T
中科院分区：
文献类型：
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作者：
Sato K;Nishiguchi KM;Maruyama K;Moritoh S;Fujita K;Ikuta Y;Kasai H;Nakazawa T
最近，局部地塞米松诱导的高眼压和随之而来的视网膜神经节细胞（RGCs）的损失已经在小鼠中被描述。这已被提出作为类固醇性青光眼的模型。在本研究中，我们在大鼠身上建立了类似的模型并进行了评估。以10周龄SD大鼠（N = 12）为研究对象，观察0.1%地塞米松（50 μl）外用3次，连用4周。另一组大鼠（N = 12）采用0.9%氯化钠作为对照组。1周后，我们观察到地塞米松治疗大鼠的体重与治疗前基线和药物治疗大鼠相比逐渐下降。与早期研究显示小鼠地塞米松注射后眼压（IOP）升高相反，局部地塞米松3周后，治疗组大鼠眼压意外下降至11.3±1.3 mmHg，而未治疗组为14.8±2.4 mmHg （P = 0.032）。治疗4周后进行的血液检查显示，与对照大鼠相比，地塞米松治疗大鼠血浆胆固醇（P < 0.001）和丙氨酸转氨酶（P = 0.019）增加了3.3倍。同时，局部类固醇不会引起血浆血糖或糖化血红蛋白（HbA1c）的变化。我们也没有检测到治疗后RGC标记物表达的变化（real-time PCR）。小鼠在局部地塞米松治疗后眼压升高，而大鼠在类似治疗后眼压反而降低。这伴随着体重的减轻而不影响血糖水平。本文的在线版本（doi:10.1186/s12952-016-0048-x）包含补充材料，可供授权用户使用。
Recently, topical dexamethasone-induced ocular hypertension and a consequent loss of retinal ganglion cells (RGCs) have been described in mice. This has been proposed as a model of steroid-induced glaucoma. In this study, we set up and evaluated a similar model in rats. Ten-week old Sprague Dawley (SD) rats (N = 12) were used to evaluate the effect of topical 0.1 % dexamethasone (50 μl) administered 3 times daily for 4 weeks. Sodium chloride (0.9 %) was used in another group of rats (N = 12) that served as the controls. After 1 week, we observed a progressive decrease in body weight in the dexamethasone-treated rats compared both to the pre-treatment baseline and the vehicle-treated rats. In contrast to earlier work that showed elevated Intraocular pressure (IOP) following dexamethasone instillation in mice, IOP in the rats unexpectedly fell to 11.3 ± 1.3 mmHg in the treated eyes, compared to 14.8 ± 2.4 mmHg in the untreated eyes, after 3 weeks of topical dexamethasone (P = 0.032). Blood tests performed after 4 weeks of treatment showed a 3.3-fold increase in both plasma cholesterol (P < 0.001) and alanine transaminase (P = 0.019) in the dexamethasone-treated rats compared to the control rats. Meanwhile, topical steroid did not induce changes in either plasma blood glucose or glycated hemoglobin (HbA1c). We also did not detect changes in the expression of RGC markers (with real-time PCR) following the treatment. In contrast to mice, which previously showed increased IOP following the topical administration of dexamethasone, the rats displayed a paradoxical reduction in IOP following a similar treatment. This was accompanied by a loss of body weight without affecting the level of blood glucose. The online version of this article (doi:10.1186/s12952-016-0048-x) contains supplementary material, which is available to authorized users.