AN ANTI-ANGIOGENIC STATE IN MICE AND HUMANS WITH RETINAL PHOTORECEPTOR CELL DEGENERATION

摘要

Neonatal mice with classic inherited retinal degeneration (Pdebrdl/Pdebrdl)are disclosed which fail to mount reactive retinal neovascularization in amouse model of oxygen-induced proliferative retinopathy. Also disclosed is acomparable human paradigm: spontaneous regression of retinalneovascularization associated with long- standing diabetes mellitus whichoccurs when retinitis pigmentosa becomes clinically evident. Both mouse andhuman data indicate that reactive retinal neovascularization either fails todevelop or regresses when the number of photoreceptor cells is markedlyreduced. The results show that a functional mechanism underlying this anti-angiogenic state is failure of the predicted up-regulation of vascularendothelial growth factor (VEGF), although other growth factors may also beinvolved. Preventive and therapeutic methods useful against both proliferativeand degenerative retinopathies are also disclosed.