Protein Kinase C Inhibitors in the Treatment of Diabetic Retinopathy. Review

M.      I. Lopez Galvez

doi:10.2174/138920111794480606

Abstract

Purpose, To review current data regarding protein Kinase C beta (PKCβ) inhibitors and its efficacy in reducing the burden of diabetic retinopathy (DR) and diabetic macular edema (DME). Data Sources, MEDLINE search (1980- 2009) and presentations to major meetings. Data Synthesis, DR and DME have emerged as the main cause of visual impairment in working age population. Treatments for DR and DME include good metabolic control, laser photocoagulation and vitrectomy. However, current therapeutic regimes have not yet provided satisfactory visual results. PKC is an intracellular signalling molecule and its activation plays an important role in the development of ocular complications and has become a field of great interest. Several PKC inhibitors have been investigated. Ruboxistaurin, an orally PKCβ inhibitor has demonstrated in vitro and in vivo benefits in dimisnish cell and blood flow alterations related to hyperglycemia and has a potential use as a therapy for DR and DME. The beneficial effect of Ruboxistaurin in them has been demonstrated in preclinical and clinical studies and controlled trials have been conducted during the last decade. The ability of Ruboxistaurin in reducing visual loss in patients with DR has been demonstrated in the PKC DRS2 trial and DME seems to respond to Ruboxistaurin with both anatomic and functional benefits. The manufacturer, Eli Lilly, has received an approvable letter from the FDA for the prevention of vision loss in patients with DR with Ruboxistaurin, but at this time the medication is not available for clinical use pending results of additional trials for this indication.

Keywords: Diabetic retinopathy, diabetic macular edema, protein kinasa, dyacilglycerol, blood flow, vascular endothelial growth factor, midosistaurin, ruboxistaurin