Rod photoreceptor dysfunction in diabetic rats is associated with decreased Na/K–ATPase activity.

Abstract

Abstract: : Purpose: To investigate the physiological consequences of reduced Na/K–ATPase activity in streptozotocin (STZ) diabetic rats. Methods: Two cohorts (n=8 each) of Sprague–Dawley rats (control and diabetic, STZ injection (50 mg/kg)) had rod electroretinogram (ERG) signals collected at 12 weeks post–diabetogenesis at three light levels (1.2–2 log cd–s.m^–2) using the method described by Nixon et al.¹ Treated rats received 2U insulin daily, and hyperglycemia was established by blood sugar levels (>15 mmol) and HbA1c. Rod (PIII) waveforms were modelled using characteristics of the phototransduction cascade² and the post–receptoral components extracted. Na/K–ATPase activity was determined spectrophotometrically from the amount of phosphate liberated in the presence or absence of ouabain. In order to quantify the effect that Na/K–ATPase inhibition has on rod photoreceptor function we applied intravitreal ouabain (3µl) injections at 5 concentrations (0.5 – 0.005 mM) in control rats, and measured the rod and cone ERG (2 log cd–s.m^–2) over a 90–minute period. Ouabain treated animals were then sacrificed and the Na/K–ATPase activity measured as detailed above. Results: At 12 weeks following STZ injection a 40% decrease (p<0.01) in the rod RmP_III was observed along with a significant decrease in Na/K–ATPase activity (–20.3%, p<0.05). Intra–vitreal injection of ouabain caused dose–related inhibition of the rod RmP_III similar to that found in the diabetic animals. No change in the sensitivity of the photoreceptoral response was observed in either ouabain treated control or STZ treated animals. Conclusions:12–week diabetic rats show abnormal ERG waveforms. In particular, the rod RmP_III is decreased in the presence of normal sensitivity. These same animals have reduced Na/K–ATPase activity. In vivo inhibition of Na/K–ATPase with ouabain gives similar ERG outcomes to the diabetic loss implying a common mechanism. 1. Nixon PJ., Bui BV., Armitage JA., Vingrys AJ. (2001) Clin Exp Ophthalmol 29: 193–6. 2. Hood DC., Birch DG. (1990) Vis Neurosci 5: 379–87.

Keywords: diabetes • NaK ATPase • photoreceptors