Photoreceptor degeneration is the hallmark of several groups of inherited neurodegenerative
diseases causing blindness in humans. These diseases are a major cause of visual handicap and to date no
satisfactory treatment is available. Here, we briefly review different approaches for the treatment of
photoreceptor degeneration, to then focus on neuroprotection.
Up to date, translation of experimental neuroprotection into a clinical setting has faced major obstacles, which
are in part due to an incomplete understanding of the regulation of pro-survival as well as neurodegenerative
mechanisms. Previous approaches were often based on the hypothesis that photoreceptor cell death was
governed by a single, apoptotic cell death mechanism. This perception has turned out too simple as recent
work has demonstrated that photoreceptor cell death is governed by non-apoptotic mechanisms as well.
Moreover, there is evidence, that several different destructive processes are executed in parallel. Briefly
reviewing the complexity of degenerative mechanisms, this review discusses relevant pathways, options to
target signaling cascades, final common denominators of cell death, and the interplay of events executing cell
death. In particular, we focus on cGMP-signaling, epigenetic and proteolytic processes and the corresponding
enzymatic activities that were recently shown to be causally related to retinal degeneration. Finally, we
illustrate how a better understanding of destructive mechanisms may enable identification and validation of
novel targets for neuroprotection, and allow development of next generation neuroprotective treatments as well
as combination therapy.