Abstract
In patients with diabetes, hyperglycemia is known to promote high levels of diacylglycerol which activates protein kinase C (PKC) in the vascular tissues and leads to the production of vascular endothelial growth factor (VEGF) in the retina. PKC activation and increased concentration of VEGF are likely to play a key role in diabetic microvascular complications, particularly change in vascular permeability, inflammation, fluid leakage and ischemia in the retina. PKC comprises a super family of isoenzymes that is activated in response to various stimuli. The PKC family consists of 12 isomers that possess distinct differences in structure, substrate requirement, expression and localization. PKC isomer selective inhibitors and VEGF trap are likely to be new therapeutics, which can delay the onset or stop the progression of diabetic vascular disease. A new promising therapy for diabetic retinopathy is undergoing Phase III trials, in which they proposed to target PKC βII isomer using Ruboxistaurin by oral administration. Besides retina, PKC βII isomer is found in higher concentration in brain, spleen, etc. So, oral targeting may be a questionable approach since generalized inhibitors may prove toxic in the treatment of diabetic retinopathy and ocular delivery may be a better alternative approach.
Keywords: Diabetic Retinopathy, PKC, VEGF, inhibitors, novel drug delivery approach
Current Drug Delivery
Title:Oral Targeting of Protein Kinase C Receptor: Promising Route for Diabetic Retinopathy?
Volume: 9 Issue: 4
Author(s): Deepa Pathak, Ankur Gupta, Bhagyashree Kamble, Gowthamarajan Kuppusamy and Bhojraj Suresh
Affiliation:
Keywords: Diabetic Retinopathy, PKC, VEGF, inhibitors, novel drug delivery approach
Abstract: In patients with diabetes, hyperglycemia is known to promote high levels of diacylglycerol which activates protein kinase C (PKC) in the vascular tissues and leads to the production of vascular endothelial growth factor (VEGF) in the retina. PKC activation and increased concentration of VEGF are likely to play a key role in diabetic microvascular complications, particularly change in vascular permeability, inflammation, fluid leakage and ischemia in the retina. PKC comprises a super family of isoenzymes that is activated in response to various stimuli. The PKC family consists of 12 isomers that possess distinct differences in structure, substrate requirement, expression and localization. PKC isomer selective inhibitors and VEGF trap are likely to be new therapeutics, which can delay the onset or stop the progression of diabetic vascular disease. A new promising therapy for diabetic retinopathy is undergoing Phase III trials, in which they proposed to target PKC βII isomer using Ruboxistaurin by oral administration. Besides retina, PKC βII isomer is found in higher concentration in brain, spleen, etc. So, oral targeting may be a questionable approach since generalized inhibitors may prove toxic in the treatment of diabetic retinopathy and ocular delivery may be a better alternative approach.
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Cite this article as:
Pathak Deepa, Gupta Ankur, Kamble Bhagyashree, Kuppusamy Gowthamarajan and Suresh Bhojraj, Oral Targeting of Protein Kinase C Receptor: Promising Route for Diabetic Retinopathy?, Current Drug Delivery 2012; 9 (4) . https://dx.doi.org/10.2174/156720112801323080
DOI https://dx.doi.org/10.2174/156720112801323080 |
Print ISSN 1567-2018 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5704 |
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