Free radical trap phenyl-N-tert-butylnitrone protects against light damage but does not rescue P23H and S334ter rhodopsin transgenic rats from inherited retinal degeneration.
Phenyl-N-tert-butylnitrone (PBN) protects rat retinas against light damage. Because the degenerative process involved in light damage and inherited retinal degeneration both lead to a common final cell death, apoptosis, we used transgenic rats with a P23H or S334ter rhodopsin mutation to test the effects of PBN on retinal degeneration and light damage and the susceptibility of the transgenic rats to light damage. In the first study, 3-week-old mutant and wild-type rats were given no drug, 0.25% PBN in drinking water, or 0.25% PBN in drinking water plus three daily intraperitoneal injections of PBN (100 mg/kg, i.p., every 8 hr). Electroretinograms were recorded at postnatal day 49, after which the rats were killed for morphometric analysis. There was no photoreceptor rescue by PBN in P23H or S334ter rats, as evidenced by equivalent loss of function and photoreceptor cells in the three treatment groups. In the second study, P23H, S334ter, and wild-type rats were exposed for 24 hr to 2700 lux light. The rats were untreated or treated with PBN (50 mg/kg per injection, every 6 hr, starting before exposure). ERGs were recorded before and 1 d after exposure. Animals were killed 6 d later for morphometric analysis. PBN protected wild-type and P23H but not S334ter retinas from light damage. S334ter retinas were relatively less susceptible to light damage than P23H and wild-type rats. The results suggest that the initiating event(s) that causes photoreceptor cell death in the mutated rats is different from that which occurs in light damage, although both ultimately undergo an apoptotic cell death.
Ranchon
Isabelle
I
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA. isabelle.ranchon@uclermont1.fr
LaVail
Matthew M
MM
Kotake
Yashige
Y
Anderson
Robert E
RE
D019943:Amino Acid Substitution; D000818:Animals; D030801:Animals, Genetically Modified; D003497:Cyclic N-Oxides; D004195:Disease Models, Animal; D004596:Electroretinography; D016166:Free Radical Scavengers / Q000494:pharmacology*; D020022:Genetic Predisposition to Disease; D008027:Light / Q000009:adverse effects*; D009154:Mutation; D009589:Nitrogen Oxides / Q000627:therapeutic use*; D010775:Photic Stimulation; D017440:Photoperiod; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D012162:Retinal Degeneration / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D012243:Rhodopsin / Q000235:genetics* / Q000378:metabolism; D012684:Sensory Thresholds / Q000528:radiation effects; D016896:Treatment Outcome
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D009589:Nitrogen Oxides; C029217:phenyl-N-tert-butylnitrone; D012243:Rhodopsin