The effects of structural plasticity at the rod and cone terminal on visual processing are not known. However, it is difficult to imagine that sprouting and differentiation of new neurites as well as retraction will not change retinal processing. Indeed, electroretinograms of human and animal degenerate retinas indicate that there are postreceptoral abnormalities (Milam et al., 1996; Banin et al., 1999), although the precise cause of these changes is not yet clear.
To preserve normal vision it may be necessary to prevent plasticity in diseases and after retinal injury. Knowing the intrinsic and external stimuli for synaptic change will make it possible to develop strategies to preserve stability. There has already been some interest in calcium channel blockers as a preventive of rod cell degeneration. Although these blockers have had mixed results regarding the delay of degeneration (Frasson et al., 1999; Pearce-Kelling et al., 2001), it would be of interest to know if they prevent synaptic plasticity since both rod and cone plasticity depends on calcium influx. Drugs which affect the NO-cGMP pathway may also, unintentionally, affect photoreceptor synapses. Viagra, for instance, which blocks PDE 5 and possibly also PDE 6 activity, increases cGMP levels and has been shown to have some effects on postreceptoral elements in the outer retina (Jagle et al., 2004). Are these drugs inducing synaptic plasticity in retinal cells? Thus both to protect normal vision and to reduce the deleterious effects of disease continued exploration of the mechanisms of plasticity is needed.
Calcium, cGMP, and cAMP have been demonstrated recently to play interconnected roles in axonal growth and guidance of cortical and spinal cord neurons in developing mammalian and amphibian CNS and in invertebrate nerve cells (Song et al., 1998; van Wagenen and Rehder, 1999; Polleux et al., 2000; van Wagenen and Rehder, 2001; Xiang et al., 2002). Increasing cyclic nucleotides can increase growth toward certain guidance molecules or make what was a repulsive guidance factor into an attractive one. The ratio of cAMP to cGMP may influence growth in developing neurons (Nishiyama et al., 2003). In addition, numerous external factors guide axonal and dendritic growth during development. These factors include molecules known as guidance factors but also chemokines and neurotransmitters (Xiang et al., 2002; Lipton and Kater, 1989). Many of the findings observed in developing nervous tissue could be easily tested in adult retina and with adult retinal neurons. Interestingly, in ferret retinal development, rod and cone cells extend long neurites, that look similar to processes extended in adulthood after injury and disease, into the inner retina (Johnson et al., 1999). As development proceeds and the outer synaptic layer forms, the processes are retracted. The ferret may provide an additional and somewhat unique model of photoreceptor plasticity. Although regeneration does not faithfully follow the details of ontogeny, it nonetheless appears that if reactive plasticity was viewed as a facet of developmental neurobiology, it would result in new and productive lines of research.
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