Berkowitz Bruce A, Bissig David, Bergman Deborah, Bercea Emanuela, Kasturi Vijaya K, Roberts Robin
Department of Anatomy and Cell Biology, Wayne State University, Detroit, MI, USA.
Mol Vis. 2011;17:2516-26. Epub 2011 Sep 27.
To test the hypothesis that intraretinal calcium channels participate in retinal morbidity in a variable oxygen (VO) model of retinopathy of prematurity.
In control and VO Long Evans (LE) rats, either untreated or treated with voltage- or ligand-gated calcium channel antagonists, we measured retinal neovascular (NV) incidence and severity (adenosine diphosphatase staining), and retinal thickness and intraretinal ion channel activity (manganese-enhanced magnetic resonance imaging). Comparisons with the commonly studied Sprague Dawley rats were performed. Visual performance (optokinetic tracking) in untreated VO LE rats was also evaluated.
In control LE rats, specific L-type voltage calcium channel antagonism, but not ligand-gated channel blockers, suppressed retinal manganese accumulation, while the inhibition of L-type channels normalized intraretinal uptake in VO LE rats. VO LE rats developed more severe NV than VO Sprague Dawley rats. Following VO, both strains demonstrated significant and similar degrees of retinal thinning and supernormal intraretinal manganese uptake. However, over time, intraretinal uptake remained elevated only in VO LE rats. Visual performance was subnormal in VO LE rats. L-type voltage-gated calcium channel antagonism reduced NV severity by 28% (p<0.05) in experimental LE rats compared to that in the control group.
Abnormal intraretinal calcium channel activity is linked with retinal morbidity in experimental retinopathy of prematurity.
在早产视网膜病变的可变氧（VO）模型中，验证视网膜内钙通道参与视网膜病变的假说。
在对照和VO长 Evans（LE）大鼠中，分别给予未治疗、电压门控或配体门控钙通道拮抗剂治疗，我们测量了视网膜新生血管（NV）发生率和严重程度（腺苷二磷酸酶染色），以及视网膜厚度和视网膜内离子通道活性（锰增强磁共振成像）。与常用的斯普拉格·道利大鼠进行了比较。还评估了未治疗的VO LE大鼠的视觉表现（视动跟踪）。
在对照LE大鼠中，特异性L型电压钙通道拮抗作用而非配体门控通道阻滞剂可抑制视网膜锰蓄积，而抑制L型通道可使VO LE大鼠的视网膜内摄取恢复正常。VO LE大鼠比VO斯普拉格·道利大鼠发生更严重的NV。VO后，两种品系均表现出显著且相似程度的视网膜变薄和视网膜内锰摄取超常。然而，随着时间推移，仅VO LE大鼠的视网膜内摄取仍保持升高。VO LE大鼠的视觉表现低于正常水平。与对照组相比，L型电压门控钙通道拮抗作用使实验性LE大鼠的NV严重程度降低了28%（p<0.05）。
视网膜内钙通道活性异常与实验性早产视网膜病变中的视网膜病变有关。
