Therefore, we bred a global Tlr4-/- deficiency state into Townes-AA mice expressing normal human adult hemoglobin A and Townes-SS mice expressing sickle hemoglobin S. We demonstrate that loss of TLR4 in SCD does not alter chronic hemolysis, but does decrease response to an acute stimulus with hemin, LPS or ischemia through loss of downstream NF-κB signaling. The gene discussed is TLR4; the disease is Schnyder corneal dystrophy.