Effect of PKCβ on retinal oxygenation response in experimental diabetes

PURPOSE. To test the hypotheses that, in mice, breathing carbogen (95% O₂-5% CO₂) oxygenates the retina better than breathing 100% oxygen, the superior hemiretinal oxygenation response to carbogen inhalation is subnormal early in diabetes, and diabetes-induced elevation of retinal protein kinase C (PKC)-β contributes to this pathophysiology. METHODS. Retinal oxygenation response (ΔPo₂) was measured using functional magnetic resonance imaging (MRI) and either carbogen or 100% oxygen inhalation challenge in C57BL/6J control (C) mice. Retinal ΔPo₂ during carbogen breathing was also measured in PKCβ knockout (C57BL6-Prkcb1; [KO]), 4 month C57BL/6J diabetic (D), and 4-month diabetic PKCβ KO (D+KO) mice. Retinal PKCβ protein expression was assessed by Western analysis. RESULTS. In C mice, retinal ΔPo₂ during carbogen breathing was significantly greater (P < 0.05) than during oxygen breathing. In D mice, ΔPo₂ during carbogen breathing was significantly lower than normal in the superior, but not the inferior, hemiretina and was normal (P > 0.0 5) in the KO group. In the D+KO mice ΔPo₂ was normal (P > 0.05) only at distances less than 1.5 mm from the optic nerve head. PKCβ expression was elevated in the retina in diabetes (P < 0.05), but was significantly decreased (P < 0.05) in D+KO mice. CONCLUSIONS. The present study confirms that, in the mouse, retinal ΔPo₂ patterns during different inhalation challenges or in the presence of diabetes are similar to what has been reported in rats. Diabetes-induced elevation of PKC appears to contribute only focally to subnormal retinal ΔPo₂. This raises the possibility that PKC inhibition therapy may be only regionally effective in treating retinal pathophysiology associated with diabetic retinopathy.