PDF(Pubmed)
Abstract：
To investigate the therapeutic effects of eye drops, namely, timolol maleate, a β-adrenergic receptor antagonist, and latanoprost, a prostaglandin F2α analog, on retinal edema in a murine retinal vein occlusion (RVO) model.
An RVO model was established using laser-induced RVO in mice, which were administered timolol maleate and latanoprost eye drops several times after venous occlusion. Subsequently, the thickness of the inner nuclear layer (INL) and the expression levels of such genes as Vegf and Atf4, which are stress markers of the endoplasmic reticulum, were examined. Primary human cultured retinal microvascular endothelial cells (HRMECs) were treated with timolol under hypoxic conditions, after which the gene expression pattern was investigated. Importantly, an integrated stress response inhibitor (ISRIB) was used in the RVO model, he known ISRIB, which suppresses the expression of ATF4 in retinal edema.
Increased INL thickness was suppressed by timolol eye drops, as were the expressions of Vegf and Atf4, in the RVO model. However, latanoprost eye drops did not induce any change in INL thickness. In HRMECs, hypoxic stress and serum deprivation increased the Vegf and Atf4 expressions; in response, treatment with timolol suppressed the Vegf expression. Furthermore, the ISRIB decreased the Vegf expression pattern and edema formation, which are associated with RVO.
These results indicate that timolol eye drops may be a potential option for RVO treatment.
An RVO model was established using laser-induced RVO in mice, which were administered timolol maleate and latanoprost eye drops several times after venous occlusion. Subsequently, the thickness of the inner nuclear layer (INL) and the expression levels of such genes as Vegf and Atf4, which are stress markers of the endoplasmic reticulum, were examined. Primary human cultured retinal microvascular endothelial cells (HRMECs) were treated with timolol under hypoxic conditions, after which the gene expression pattern was investigated. Importantly, an integrated stress response inhibitor (ISRIB) was used in the RVO model, he known ISRIB, which suppresses the expression of ATF4 in retinal edema.
Increased INL thickness was suppressed by timolol eye drops, as were the expressions of Vegf and Atf4, in the RVO model. However, latanoprost eye drops did not induce any change in INL thickness. In HRMECs, hypoxic stress and serum deprivation increased the Vegf and Atf4 expressions; in response, treatment with timolol suppressed the Vegf expression. Furthermore, the ISRIB decreased the Vegf expression pattern and edema formation, which are associated with RVO.
These results indicate that timolol eye drops may be a potential option for RVO treatment.
摘要：
■为了研究滴眼液的治疗效果，即,马来酸噻吗洛尔,β-肾上腺素能受体拮抗剂，还有拉坦前列素,前列腺素F2α类似物，小鼠视网膜静脉阻塞（RVO）模型中的视网膜水肿。
■使用激光诱导的小鼠RVO建立RVO模型，静脉闭塞后多次给予马来酸噻吗洛尔和拉坦前列素滴眼液。随后，内核层（INL）的厚度和Vegf和Atf4等基因的表达水平，这些基因是内质网的应激标记，进行了检查。在低氧条件下用噻吗洛尔处理原代人培养的视网膜微血管内皮细胞（HRMEC），之后研究了基因表达模式。重要的是,在RVO模型中使用了综合应激反应抑制剂(ISRIB)，他认识ISRIB,抑制ATF4在视网膜水肿中的表达。
■噻吗洛尔滴眼液抑制了INL厚度的增加，在RVO模型中，Vegf和Atf4的表达式也是如此。然而,拉坦前列素滴眼液没有引起INL厚度的任何变化。在HRMEC中，低氧应激和血清剥夺增加了Vegf和Atf4的表达；作为响应，噻吗洛尔治疗抑制了Vegf表达。此外，ISRIB降低了Vegf表达模式和水肿形成，与RVO相关联。
■这些结果表明，噻吗洛尔滴眼液可能是RVO治疗的潜在选择。
■使用激光诱导的小鼠RVO建立RVO模型，静脉闭塞后多次给予马来酸噻吗洛尔和拉坦前列素滴眼液。随后，内核层（INL）的厚度和Vegf和Atf4等基因的表达水平，这些基因是内质网的应激标记，进行了检查。在低氧条件下用噻吗洛尔处理原代人培养的视网膜微血管内皮细胞（HRMEC），之后研究了基因表达模式。重要的是,在RVO模型中使用了综合应激反应抑制剂(ISRIB)，他认识ISRIB,抑制ATF4在视网膜水肿中的表达。
■噻吗洛尔滴眼液抑制了INL厚度的增加，在RVO模型中，Vegf和Atf4的表达式也是如此。然而,拉坦前列素滴眼液没有引起INL厚度的任何变化。在HRMEC中，低氧应激和血清剥夺增加了Vegf和Atf4的表达；作为响应，噻吗洛尔治疗抑制了Vegf表达。此外，ISRIB降低了Vegf表达模式和水肿形成，与RVO相关联。
■这些结果表明，噻吗洛尔滴眼液可能是RVO治疗的潜在选择。
