Institute of Experimental Ophthalmology, School of Medicine, University Clinics Münster and Interdisciplinary Centre for Clinical Research (IZKF), Münster, Germany.
PLoS One. 2012;7(7):e33593. doi: 10.1371/journal.pone.0033593. Epub 2012 Jul 5.
Examination of the response of the retinal proteome to elevated intraocular pressure (IOP) and to the pharmacological normalization of IOP is crucial, in order to develop drugs with neuroptorective potential. We used a hereditary rat model of ocular hypertension to lower IOP with travaprost and dorzolamide applied topically on the eye surface, and examine changes of the retinal proteome. Our data demonstrate that elevated IOP causes alterations in the retinal protein profile, in particular in high-mobility-group-protein B1 (HMGB1), calmodulin, heat-shock-protein (HSP) 70 and carbonic anhydrase II expression. The changes of the retinal proteome by dorzolamide or travoprost are different and independent of the IOP lowering effect. This fact suggests that the eye drops exert a direct IOP-independent effect on retinal metabolism. Further investigations are required to elucidate the potential neuroprotective mechanisms signaled through changes of HMGB1, calmodulin, HSP70 and carbonic anhydrase II expression in glaucoma. The data may facilitate development of eye drops that exert neuroprotection through direct pharmacological effect.
检查视网膜蛋白质组对眼内压升高（IOP）和 IOP 的药物正常化的反应对于开发具有神经保护潜力的药物至关重要。我们使用遗传性高眼压大鼠模型，通过局部应用曲伏前列素和多佐胺来降低 IOP，并检查视网膜蛋白质组的变化。我们的数据表明，升高的 IOP 导致视网膜蛋白谱发生改变，特别是高迁移率族蛋白 B1（HMGB1）、钙调蛋白、热休克蛋白（HSP）70 和碳酸酐酶 II 的表达发生改变。多佐胺或曲伏前列素引起的视网膜蛋白质组变化是不同的，且与降低 IOP 的作用无关。这一事实表明，眼药水对视网膜代谢具有直接的、与 IOP 无关的作用。需要进一步研究阐明通过 HMGB1、钙调蛋白、HSP70 和碳酸酐酶 II 表达变化在青光眼信号转导中的潜在神经保护机制。这些数据可能有助于开发通过直接药理作用发挥神经保护作用的眼药水。
