Preventing retinal detachment-associated photoreceptor cell loss in Bax-deficient mice.
OBJECTIVE
To characterize photoreceptor cell apoptosis and cell loss in a mouse model of experimental retinal detachment (RD), and to use the technology of mouse genetics to study the molecular mechanisms underlying RD-associated photoreceptor degeneration.


METHODS
Retinal detachments were created in adult wild-type and Bax-deficient mice by subretinal injection of 1.4% sodium hyaluronate. At 1, 3, 7, and 28 days after injection, animals were killed, eyes enucleated, and retinal sections studied by histochemistry, immunofluorescence labeling, and confocal microscopy. Rods and cones were labeled, and apoptotic cells were identified with terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Photoreceptor cell apoptosis and cell loss were assessed quantitatively by counting both surviving and TUNEL-positive rods and cones.


RESULTS
TUNEL-positive cells were found within the outer nuclear layer (ONL) of the detached portions of the retina. They were detected in the detached retina on day 1, peaked on day 3, and dropped precipitously after day 7 after RD. Photoreceptor cell loss of both rods and cones followed a similar time course after RD. Moreover, deletion of the proapoptotic gene Bax in a knockout mouse model abolished the RD-associated photoreceptor cell degeneration.


CONCLUSIONS
Apoptosis is a major mechanism leading to photoreceptor cell death after RD. Blockage of the activity of the proapoptotic molecule Bax in a knockout mouse model prevents photoreceptor cell apoptosis and cell loss. These data suggest that the Bax-mediated apoptotic signaling pathway plays a critical role in RD-associated photoreceptor cell death.
Yang
Liu
L
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
Bula
Deisy
D
Arroyo
Jorge G
JG
Chen
Dong F
DF
D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D004195:Disease Models, Animal; D019084:Fluorescent Antibody Technique, Indirect; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D012162:Retinal Degeneration / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D012163:Retinal Detachment / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein