Transcriptional Role of Pyruvate Kinase M2 Isoform in Diabetic Retinopathy
The main therapeutic goal for diabetic retinopathy (DR) is to prevent vision loss in patients with diabetes mellitus. Identifying the visual complications at a preclinical juncture will offer an early therapeutic window for diagnosis and intervention. Very recently, we found that the pyruvate kinase M2 isoform (PKM2) regulates visual function through the regulation of a key enzyme, phosphodiesterase 6β (Pde6β), involved in modulating photoreceptor functions. In DR, PKM2 and Pde6β expression and visual function are reduced. PKM2 is a glycolytic enzyme and a transcriptional co-activator. We are studying the molecular mechanism of PKM2-regulated Pde6β expression in DR.
Role of Protein Tyrosine Phosphatase 1B (PTP1B) in Diabetic Retinopathy
Neurodegeneration is an important component of DR, as demonstrated by increased neural apoptosis in the retina during experimental and human diabetes. Insulin receptor (IR) activation has been shown to rescue retinal neurons from apoptosis through a phosphoinositide 3-kinase cascade. Retinal IR is constitutively active; however, this constitutive activation is impaired in DR. The state of IR activation is tightly regulated by protein tyrosine phosphatase 1B (PTP1B). Studies are underway in our laboratory to understand the role of PTP1B in the regulation of retinal IR activity.