The Potential Role of PKC in Diabetic Retinopathy

Diabetic retinopathy is one of the most debilitating complications of diabetes mellitus. Despite major advances in understanding the pathogenesis of this disease and the efficacy of current therapies, diabetic retinopathy remains the leading cause of new-onset blindness among working-age people. The mainstay of current therapy, laser photocoagulation, is useful in preventing blindness and severe vision loss but is not often effective in restoring lost visual acuity. In addition, troublesome side effects and potentially serious complications may occur. Diabetic retinopathy is characterized by a pro-gression of abnormalities. Nonproliferative retinopathy results from a series of biochemical and cellular changes that ultimately cause progressive retinal ischemia. The subsequent elaboration of growth fac-tors in response to ischemia leads to the development of proliferative retinopathy, which is character-ized by aberrant neovacularization of the retina—potentially leading to severe, irreversible visual loss. Increased retinal vascular leakage may also occur at any stage in this process, resulting in macular edema and possible progressive visual impairment. Although numerous biochemical factors are thought to play a role in the development of retinopathy, activation of protein kinase C (PKC), specifi-cally the beta isoform of PKC (PKC), is implicated for both the early and late-stage manifestations of retinopathy. Studies suggest that orally administered LY333531,