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.
