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J.A. Phipps, A.E. Weymouth, E.L. Fletcher, A.J. Vingrys; Rod photoreceptor dysfunction in diabetic rats is associated with decreased Na/K–ATPase activity. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3233.
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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 RmPIII 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 RmPIII 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 RmPIII 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.
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