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 progression of abnormalities. Nonproliferative retinopathy results from a series of biochemical and cellular changes that ultimately cause progressive
retinal ischemia. The subsequent elaboration of
growth factors in response to
ischemia leads to the development of proliferative retinopathy, which is characterized 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), specifically the beta
isoform of PKC (
PKC beta), is implicated for both the early and late-stage manifestations of retinopathy. Studies suggest that orally administered LY333531, a beta-
isoform specific PKC inhibitor, may be effective in ameliorating retinopathy progression, proliferation, and
retinal vascular leakage. The status of ongoing clinical trials aimed at addressing the efficacy of
PKC beta with regard to diabetes-induced
retinal complications and perspectives on the role of
PKC beta are presented.