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1From the Departments of Anatomy and Cell Biology and 3Ophthalmology, Wayne State University, Detroit, Michigan; and 2Max-Planck-Institut für Experimental Endokrinologie, Hannover, Germany.
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)-ß contributes to this pathophysiology.
METHODS. Retinal oxygenation response (
PO2) was measured using functional magnetic resonance imaging (MRI) and either carbogen or 100% oxygen inhalation challenge in C57BL/6J control (C) mice. Retinal
PO2 during carbogen breathing was also measured in PKCß knockout (C57BL6-Prkcb1; [KO]), 4 month C57BL/6J diabetic (D), and 4-month diabetic PKCß KO (D+KO) mice. Retinal PKCß protein expression was assessed by Western analysis.
RESULTS. In C mice, retinal
PO2 during carbogen breathing was significantly greater (P < 0.05) than during oxygen breathing. In D mice,
PO2 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
PO2 was normal (P > 0.05) only at distances less than 1.5 mm from the optic nerve head. PKCß 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
PO2 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
PO2. This raises the possibility that PKC inhibition therapy may be only regionally effective in treating retinal pathophysiology associated with diabetic retinopathy.
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