DNA repair in photoreceptor survival.
Light triggers a sequence of events that damage photoreceptor cells within the superior central portion of the retina, resulting in apoptotic cell death. This damage is mediated by energy absorbed by rhodopsin and the intermediates of the rhodopsin-bleaching process. Furthermore, inhibition of the visual cycle and the re-isomerization of all-trans retinol preserve photoreceptors. We have recently shown light-induced DNA fragmentation to occur only within photoreceptors, and, in time-courses following light treatment, these cells exhibit two peaks of damage, approx 24 h apart. This was also observed by quantification of nucleosome-length DNA fragments and their multimers (DNA ladders) as well as by highly repetitive short interspersed nuclear element (SINE) analysis. This bimodal pattern of photoreceptor DNA fragmentation suggests two populations of cells, and each of these were affected by light at a different rate or time. However, the rat retina is composed of 500 nm-sensitive rods, and approx 2% cones, suggesting that a two-cell-type hypothesis is incorrect. Thus, there is a possibility that light-induced DNA fragmentation is triggered and that some photoreceptors are able to initiate a repair mechanism, resulting in a temporary decrease in DNA damage followed by another wave of fragmentation that ultimately leads to cell death. Subsequently, we observed that the repair enzyme DNA polymerase beta was upregulated following light treatment, again suggesting the presence of a repair mechanism. Our results suggest that a DNA-repair mechanism exists within photoreceptors, and indicate that manipulation of this process may provide additional protection and/or recovery from events that trigger DNA fragmentation and apoptotic cell death in photoreceptors.
Neuroscience Center of Excellence and Department of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
M Soledad
MS
Cortina
William C
WC
Gordon
Walter J
WJ
Lukiw
Nicolas G
NG
Bazan
D000818:Animals; D002470:Cell Survival / Q000235:genetics; D053938:DNA Fragmentation / Q000235:genetics*; D019951:DNA Polymerase beta / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D004195:Disease Models, Animal; D006801:Humans; D010775:Photic Stimulation / Q000009:adverse effects*; D010786:Photoreceptor Cells / Q000378:metabolism* / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology
D019951:DNA Polymerase beta