Visual deficits caused by abnormal visual experience during development are hard to recover in adult animals. Removal of chondroitin sulfate proteoglycans from the mature extracellular matrix with chondroitinase ABC promotes plasticity in the adult visual cortex. We tested whether chondroitinase ABC treatment of adult rats facilitates anatomical, functional, and behavioral recovery from the effects of a period of monocular deprivation initiated during the critical period for monocular deprivation. We found that chondroitinase ABC treatment coupled with reverse lid-suturing causes a complete recovery of ocular dominance, visual acuity, and dendritic spine density in adult rats. Thus, manipulations of the extracellular matrix can be used to promote functional recovery in the adult cortex.amblyopia ͉ chondroitin sulfate ͉ extracellular matrix ͉ glycosaminoglycan ͉ plasticity A n abnormal visual experience during development results in defective visual function. For instance, cataract or anisometropia in early childhood leads to a condition of reduced visual acuity (amblyopia) that can be fully recovered only if the treatment of these conditions is performed during early infancy (1). The lack of substantial recovery from amblyopia in the adult has been attributed to a decline in the plasticity of cortical circuits occurring during late postnatal development. Indeed, studies in animals have shown that monocular deprivation (MD) impairs visual cortical responses to the deprived eye and affects axonal morphology and dendritic spine density only if performed during a critical period of postnatal development (2-6). The ability to recover from the deficits induced by MD declines with age; reopening the previously deprived eye or reverse lidsuturing (RS) in young animals results in full recovery of ocular dominance, but these procedures become progressively less effective with age and are practically ineffective in the adult (7-9). Recovery from the amblyopic effect of MD is also progressively less efficient during development. In the adult, visual acuity shows small recoveries even if its final level continues to be pathologically low (10, 11). Similarly, a limited recovery of visual acuity can also be observed in adult amblyopic patients in particular conditions (1), although visual acuity remains largely abnormal.These observations suggest that the adult visual cortex expresses factors that inhibit experience-dependent plasticity and that develop in conjunction with the end of the critical period. The molecular identity of these factors is only partially known (12); studies performed in rodents have attributed the closure of the critical period to the maturation of inhibitory intracortical circuitry (13,14) and to developmental changes in the expression of molecular factors regulating synaptic plasticity (15, 16). Recently, it has been shown that at least part of the low level of plasticity of the adult visual cortex is due to the condensation of extracellular matrix molecules in perineuronal nets (PNNs). Indeed, chondr...