ABSTRACT
Studies of programmed cell death in the developing retina in vitro are currently reviewed. The results of inhibiting protein synthesis in retinal explants indicate two mechanisms of apoptosis. One mechanism depends on the synthesis of positive modulators ('killer proteins'), while a distinct, latent mechanism appears to be continuously blocked by negative modulators. Extracellular modulators of apoptosis include the neurotrophic factors NT-4 and BDNF, while glutamate may have either a positive or a negative modulatory action on apoptosis. Several protein kinases selectively modulate apoptosis in distinct retinal layers. Calcium and nitric oxide were also shown to affect apoptosis in the developing retianl tissue. The protein c-Jun was found associated with apoptosis in various circumstances, while p53 seems to be selectively expressed in some instances of apoptosis. The results indicate that the sensitivity of each retinal cell to apoptosis is controlled by multiple, interactive, cell type- and context-specific mechanisms. Apoptosis in the retina depends on a critical interplay of extracellular signals delivered through neurotrophic factors, neurotransmitters and neuromodulators, several signal transduction pathways, and the expression of a variety of genes.
Subject(s)
Mice , Rats , Animals , Apoptosis/physiology , Brain-Derived Neurotrophic Factor/physiology , Culture Techniques , In Vitro Techniques , Retinal Degeneration/metabolism , Signal Transduction/physiologyABSTRACT
The axon orientation and axo-dendritic polarities of ganglion cells were investigated in the retinae of developing and adult rats labeled with retrograde tracers. The cells were classified as either regular, if both parameters corresponded to those found among the majority of ganglion cells in the retina of adult rats, or irregular, if either axon orientation or axo-dentritic polarity, or both to follow the norm of adult retinae. The number of regular cells declined from 118,000 to the adult value of 63,000 during the first 5 days following birth, while the number of irregular cells remained stable at 90,000-100,000 during this period and declined thereafter to 46,000. These data suggest that the geometry of neurites within the retina affect the selective elimination of ganglion cells during postnatal development in rats