Photoreceptor outer segment phagocytosis attenuates oxidative stress-induced apoptosis with concomitant neuroprotectin D1 synthesis.
Photoreceptor cell (rods and cones) renewal is accompanied by intermittent shedding of the distal tips of the outer segment followed by their phagocytosis in the retinal pigment epithelial (RPE) cells. This renewal is essential for vision, and it is thought that it fosters survival of photoreceptors and of RPE cells. However, no specific survival messenger/mediators have as yet been identified. We show here that photoreceptor outer segment (POS) phagocytosis markedly attenuates oxidative stress-induced apoptosis in ARPE-19 cells in culture. This phenomenon does not seem to be a generalized outcome of phagocytosis because nonbiological (polystyrene microsphere) phagocytosis did not elicit protection. The free docosahexaenoic acid (DHA) pool size and neuroprotectin D1 (NPD1) content increased during POS phagocytosis but not during microspheres phagocytosis. We have also explored other lipid mediators [lipoxin A4 and 15(S)- and 12(S)-hydroxyeicosatetraenoic acids] under these conditions and found them unchanged upon POS phagocytosis. Moreover, oxidative stress challenge to RPE cells undergoing POS phagocytosis further increased DHA and NPD1 content. Under these conditions, NPD1 was found within the RPE cells as well as in the culture medium, suggesting autocrine and paracrine bioactivity. Furthermore, using deuterium-labeled DHA, we show that as the availability of free DHA increases during oxidative stress, NPD1 synthesis is augmented in ARPE-19 cells. Our data suggest a distinct signaling that promotes survival of photoreceptor and RPE cells by enhancing the synthesis of NPD1 during phagocytosis. Taken together, NPD1 may be a mediator that promotes homeostatic regulation of cell integrity during photoreceptor cell renewal.
Neuroscience Center and Department of Ophthalmology, Louisiana State University Health Sciences Center School of Medicine, New Orleans, LA 70112, USA.
Pranab K
PK
Mukherjee
Victor L
VL
Marcheselli
Juan Carlos
JC
de Rivero Vaccari
William C
WC
Gordon
Fannie E
FE
Jackson
Nicolas G
NG
Bazan
D017209:Apoptosis; D002460:Cell Line; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D006801:Humans; D008863:Microspheres; D018384:Oxidative Stress; D010587:Phagocytosis; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D011137:Polystyrenes; D012374:Rod Cell Outer Segment / Q000502:physiology*
D011137:Polystyrenes; C487679:protectin D1; D004281:Docosahexaenoic Acids