Cellular Pathway Implicated in Diabetic Retinopathy
Study suggests it is independent of another signaling pathway activated by hyperglycemia
FRIDAY, Nov. 6 (HealthDay News) -- An additional cellular signaling pathway activated by hyperglycemia is involved in the death of retinal cells that lead to diabetic retinopathy, according to a study published online Nov. 1 in Nature Medicine.
Noting that the platelet-derived growth factor (PDGF) signaling pathway has been implicated in the death of retinal pericytes and the formation of acellular capillaries responsible for diabetic complications, Pedro Geraldes, Ph.D., from the Joslin Diabetes Center in Boston, and colleagues investigated whether this pathway was involved in pericyte death induced by hyperglycemia.
The researchers found that hyperglycemia activated a PKC-δ signaling pathway that eventually led to inhibition of PDGF receptor-β and retinal pericyte death. Retinas from diabetic mice had increased PKC-δ activity and an increased number of acellular capillaries, which was not reversible by insulin treatment. Retinas from diabetic mice lacking PKC-δ did not show PDGF receptor-β inhibition or acellular capillaries. This pathway was independent of the NF-κB pathway, which had been previously shown to be involved in pericyte death induced by hyperglycemia.
"These findings elucidate a new signaling pathway by which hyperglycemia can induce PDGF resistance and increase vascular cell apoptosis to cause diabetic vascular complications," Geraldes and colleagues conclude.