Intense light triggers cell death in cones and rods by two distinct mechanisms: rapid, necrosis-like cell death occurs in cones; prolonged, apoptotic death is displayed by rods. However, the areas of cone and rod loss coincide, suggesting some interrelationship. DNA fragmentation in rods occurs in two waves. Our evidence suggests a repair mechanism that triggers up-regulation of the enzyme DNA polymerase beta, implying a rod-specific mechanism that initially attempts DNA repair, but which subsequently fails, resulting in a second wave of damage leading to apoptotic rod cell death. This study suggests two different but coincidental pathways lead to photoreceptor death. Definition of these two pathways could suggest useful pharmacologic sites toward which compounds could be targeted to promote cell survival in damaging retinal degenerative diseases. In addition, maintenance or enhancement of existing in-house repair mechanisms could provide additional approaches for the rescue of neurons with stress-induced nuclear damage.