Abstract :
PURPOE: To review the evidence upporting a role for the beta (β) ioform of protein kinae C (PKC) in the pathogenei of diabetic retinopathy and the poible therapeutic benefit of inhibiting thi enzyme.
DEIGN: Brief literature review of reearch uggeting the potential ue for ytemic inhibitor of the β ioform of PKC a a medical therapy to prevent the progreion of diabetic retinopathy. Brief conideration i given to previou, primarily clinical, tudie dealing with other therapie for thi dieae.
REULT: Kinae tranfer the terminal, “high energy,” phophate group of ATP to a ite on a target protein, thereby activating the protein, which may be an enzyme, cell membrane receptor, or ion tranport channel. The PKC family i a group of uch enzyme that require pecific activator molecule, including diacylglycerol, whoe intracellular concentration i ubtantially increaed during the hyperglycemia of diabete. Protein kinae Cβ i preent at high level in the retina. Increaed activation of thi enzyme, perhap by producing tiue hypoxia, lead to increaed expreion of vacular endothelial growth factor, a mitogen that increae proliferation of vacular endothelial cell leading to neovacularization and enhance breakdown of the blood-retinal barrier, perhap reulting in macular edema.
CONCLUION: By interfering with the above biochemical pathway, PKC inhibitor may retard or prevent the development and progreion of diabetic retinopathy. Becaue member of the PKC family are found throughout the body, a generalized inhibitor i likely to be toxic. However, an inhibitor pecific for PKCβ may act effectively within the retina and have a favorable toxicity profile. Two phae III randomized controlled clinical trial of uch an inhibitor are now in progre, attempting to evaluate the efficacy of thi approach to preventing the progreion, or inducing regreion, of “nonclinically ignificant” diabetic macular edema and of evere nonproliferative diabetic retinopathy.
