Photoreceptor stability and degeneration in mammalian retina: Lessons from the edge

Surveys of the human retina have reported the degeneration of the anterior edge of the retina to be a common feature (Vrabec 1967; Gartner 1975; Gartner and Henkind 1981; Ahnelt 1998), sufficiently common in older humans to be regarded as normal. Detailed observations of mouse and rat retina have suggested that these degenerative phenomena begin very early in postnatal life (Mervin and Stone 2002a, 2002b), with a period of localized photoreceptor death. Conversely, in experimental studies of photoreceptor degeneration in adult rodents, the edge of the retina has been described as highly resistant to degeneration,whether light- or mutation- induced (LaVail 1981; Valter et al. 1998; Bowers et al. 2001). This paradox, that a chronically degenerative region of retina is resistant to acute stress, has been reproduced in studies of pre-conditioning of the retina, in which limited damage to the retina (including some photoreceptor death) upregulates protective mechanisms which make the surviving photoreceptors resistant to subsequent stress (Liu et al. 1998; Nir et al. 1999; Cao et al. 2001). The same paradox is evident in the impact of ambient light levels on photoreceptor structure and vulnerability (Penn and Anderson 1991). Bright ambient light kills some photoreceptors and makes the survivors resistant to acute stress. Penn and Andersons data make clear that degenerative and stabilizing properties appeared in the same cell, photoreceptors exposed to stress showing degenerative membrane changes, yet proving highly resistant to light challenge. This chapter summarises results of studies of degenerative phenomena at the edge of the retina. Taken together, these observations suggest that the edge of the retina is subject throughout life to a localized stress, which in-duces a progressive degenerative process. These edge-specific changes are part of the life history of the normal retina, and form part of the baseline against which the retinal degenerations take place.