Intraretinal calcium channels and retinal morbidity in experimental retinopathy of prematurity

• Published in: Molecular vision Vol. 17; pp. 2516 - 2526
• Main Authors: Berkowitz, Bruce A, Bissig, David, Bergman, Deborah, Bercea, Emanuela, Kasturi, Vijaya K, Roberts, Robin
• Format: Journal Article
• Language: English
• Published: United States Molecular Vision 27-09-2011
• Subjects: Animals; Calcium - antagonists & inhibitors; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium Channels - metabolism; Disease Models, Animal; Humans; Infant, Newborn; Ligand-Gated Ion Channels - antagonists & inhibitors; Ligand-Gated Ion Channels - metabolism; Magnetic Resonance Imaging; Manganese - metabolism; Optometry; Oxygen - metabolism; Rats; Rats, Long-Evans; Rats, Sprague-Dawley; Retina - drug effects; Retina - metabolism; Retina - pathology; Retinal Neovascularization - metabolism; Retinal Neovascularization - pathology; Retinopathy of Prematurity - metabolism; Retinopathy of Prematurity - pathology; Retinopathy of Prematurity - physiopathology
• ISSN: 1090-0535; 1090-0535

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.