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Beta2 adrenergic receptor silencing change intraocular pressure in New Zealand rabbits

机译:Beta2肾上腺素能受体沉默改变新西兰兔眼内压

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Purpose/aim Glaucoma consists of a group of progressive optic neuropathies that are characterized by degeneration of the optic nerve and irreversible visual filed loss. Elevated intraocular pressure is the only proven treatable risk factor and commercial products used for glaucoma treatment are focused in lowering intraocular pressure. These drugs can have various undesirable side effects and this invites to look for new strategies. The purpose of this work is to study the use of a siRNA (small interfering RNA) to selectively silence beta2 adrenergic receptors and to see whether it reduces IOP (intraocular pressure). Material and methods Topical instillation of beta2 adrenergic receptors small-interfering RNA (siRNA, 25–250?μg) was applied and IOP was measured with a Tonopen XL up to 9 consecutive days. The effect of such siRNA was compared to commercial compounds such as Timoftlol, Trusopt and Xalatan, and it was also analyzed if some anatomical changes occurred by microscopy. Results siRNA designed for beta2 adrenergic receptor induced a reduction of intraocular pressure (IOP) of 30?±?5%, compared to a control (scrambled siRNA). The results in terms of IOP decrease were similar to that found with commercial compounds but a long-lasting hypotensive action was shown by beta2 adrenergic receptor siRNA treatment as compared to commercial drugs. No apparent side effects were observed in the ocular structures. Conclusion The use of siRNA against the beta2 adrenergic receptors could provide an interesting therapeutic strategy for glaucoma treatment.
机译:目的/目的青光眼由一组进行性视神经病变组成,其特征在于视神经变性和不可逆的视场丧失。升高的眼内压是唯一被证明可治疗的危险因素,用于青光眼治疗的商业产品集中于降低眼内压。这些药物可能会产生各种不良副作用,因此需要寻找新的策略。这项工作的目的是研究使用siRNA(小干扰RNA)选择性沉默β2肾上腺素能受体并观察其是否降低IOP(眼压)。材料和方法局部滴加β2肾上腺素受体小干扰RNA(siRNA,25–250μg),并使用Tonopen XL连续9天测量IOP。将这种siRNA的作用与诸如Timoftlol,Trusopt和Xalatan的市售化合物进行了比较,并且还通过显微镜检查了是否发生了某些解剖学变化。结果与对照组(混乱的siRNA)相比,为β2肾上腺素能受体设计的siRNA引起的眼内压(IOP)降低了30%±5%。就IOP降低而言,结果与市售化合物相似,但与市售药物相比,β2肾上腺素能受体siRNA治疗显示出持久的降压作用。在眼结构中未观察到明显的副作用。结论针对β2肾上腺素受体的siRNA的使用可以为青光眼的治疗提供有趣的治疗策略。

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