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  Effect of PKCbeta on retinal oxygenation response in experimental diabetes.

Luan, H., Leitges, M., Gupta, R. R., Pacheco, D., Seidner, A., Liggett, J., et al. (2004). Effect of PKCbeta on retinal oxygenation response in experimental diabetes. Investigative Ophthalmology and Visual Science, 45(3), 937-942. Retrieved from http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14985314.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0012-EE2A-6 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0029-68C0-B
Genre: Journal Article

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 Creators:
Luan, H., Author
Leitges, M.1, Author              
Gupta, R. R., Author
Pacheco, D., Author
Seidner, A., Author
Liggett, J., Author
Ito, Y., Author
Kowluru, R., Author
Berkowitz, B. A., Author
Affiliations:
1Department of Genes and Behavior, MPI for biophysical chemistry, Max Planck Society, ou_persistent34              

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Free keywords: Administration, Inhalation; Animals; Blotting, Western; Carbon Dioxide/administration and dosage; Diabetes Mellitus, Experimental/metabolism; Diabetic Retinopathy/metabolism; Disease Models, Animal; Isoenzymes/genetics/metabolism; Magnetic Resonance Imaging; Mice; Mice, Inbred C57BL; Mice, Knockout; Oxygen/administration & dosage; Oxygen Consumption/physiology; Protein Kinase C/genetics/*metabolism; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Retina/enzymology/physiology
 Abstract: PURPOSE: 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.

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Language(s): eng - English
 Dates: 2004-03
 Publication Status: Published in print
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 Rev. Method: Peer
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Title: Investigative Ophthalmology and Visual Science
Source Genre: Journal
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Pages: - Volume / Issue: 45 (3) Sequence Number: - Start / End Page: 937 - 942 Identifier: -