Delay of photoreceptor cell degeneration in rd mice by systemically administered phenyl-N-tert-butylnitrone.
OBJECTIVE
To study the effect of systemic administration of phenyl-N-tert-butylnitrone (PBN) on the degeneration of photoreceptor cells in rd mice.


METHODS
PBN was injected intraperitoneally into FVB/rd mice on postnatal days (P) 5 to 14 (group A), and P10 to 18 (group B). At days P14, 16, 18, 20 and 27, morphological changes and apoptosis were analyzed by staining with hematoxylin and eosin or DAPI. The effect of PBN on apoptosis was analyzed in retinal pigment epithelial (RPE) cells by the measurement of caspase-3 activity.


RESULTS
In control and group B mice, the outer nuclear layer (ONL) of the retina was composed of 8-10 rows at P12, and rapidly decreased to one row at P18. In group A mice, the ONL was preserved with 5-7 rows at P18, and decreased to one row at P22. PBN inhibited caspase-3 activity in cultured RPE cells.


CONCLUSIONS
PBN delayed, but did not block, the degeneration of photoreceptor cells in rd mice. PBN may exert its inhibitory effect during the early phase of photoreceptor cell degeneration.
Department of Ophthalmology, Seoul National University College of Medicine, Seoul Artificial Eye Center & Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.
Jin Hyoung
JH
Kim
Jeong Hun
JH
Kim
Young Suk
YS
Yu
Seon Mi
SM
Jeong
Kyu-Won
KW
Kim
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D003497:Cyclic N-Oxides; D004195:Disease Models, Animal; D004792:Enzyme Precursors / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D016166:Free Radical Scavengers / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009589:Nitrogen Oxides / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D003497:Cyclic N-Oxides; D004792:Enzyme Precursors; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D009589:Nitrogen Oxides; C029217:phenyl-N-tert-butylnitrone; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases