Effect of PKCbeta on retinal oxygenation response in experimental diabetes.
OBJECTIVE
To test the hypotheses that, in mice, breathing carbogen (95% O(2)-5% CO(2)) 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)-beta contributes to this pathophysiology.


METHODS
Retinal oxygenation response (DeltaPO(2)) was measured using functional magnetic resonance imaging (MRI) and either carbogen or 100% oxygen inhalation challenge in C57BL/6J control (C) mice. Retinal DeltaPO(2) during carbogen breathing was also measured in PKCbeta knockout (C57BL6-Prkcb1; [KO]), 4 month C57BL/6J diabetic (D), and 4-month diabetic PKCbeta KO (D+KO) mice. Retinal PKCbeta protein expression was assessed by Western analysis.


RESULTS
In C mice, retinal DeltaPO(2) during carbogen breathing was significantly greater (P < 0.05) than during oxygen breathing. In D mice, DeltaPO(2) 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 DeltaPO(2) was normal (P > 0.05) only at distances less than 1.5 mm from the optic nerve head. PKCbeta 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 DeltaPO(2) 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 DeltaPO(2). This raises the possibility that PKC inhibition therapy may be only regionally effective in treating retinal pathophysiology associated with diabetic retinopathy.
Departments of Anatomy and Cell Biology, Wayne State University, Detroit, Michigan 48201, USA.
Hongmei
H
Luan
Michael
M
Leitges
Rita R
RR
Gupta
Daniel
D
Pacheco
Andres
A
Seidner
Jessica
J
Liggett
Yasuki
Y
Ito
Renu
R
Kowluru
Bruce A
BA
Berkowitz
D000280:Administration, Inhalation; D000818:Animals; D015153:Blotting, Western; D002245:Carbon Dioxide / Q000008:administration & dosage; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000378:metabolism; D004195:Disease Models, Animal; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010100:Oxygen / Q000008:administration & dosage; D010101:Oxygen Consumption / Q000502:physiology*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D064546:Protein Kinase C beta; D012160:Retina / Q000201:enzymology / Q000502:physiology*
D007527:Isoenzymes; D002245:Carbon Dioxide; C011700:carbogen; C579056:Prkcb protein, rat; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D010100:Oxygen