Minocycline delayed photoreceptor death in rds mice through iNOS-dependent mechanism.
OBJECTIVE
To elucidate the role of activated microglia and nitric oxide (NO) in photoreceptor apoptosis in rds mice, and to investigate the effect of minocycline treatment on rds mice.


METHODS
Photoreceptor apoptosis in rds mice was detected by terminal dUTP transferase nick end labeling (TUNEL). Retinal microglial cells were identified by CD11b antibody. The mRNA expression of inducible nitric oxide synthase (iNOS) and chemokines were examined by reverse transcription polymerase chain reaction (RT-PCR) assay. The protein expression of iNOS was examined by immunohistochemistry and Western blotting analysis. The rds mice were treated intra-peritoneally from the second postnatal day (P2) with minocycline.


RESULTS
Accompanying photoreceptor degeneration in rds mice, microglia were activated and immigrated from inner retinal layer (IRL) to outer nuclear layer (ONL), and the expression of iNOS was up-regulated. Minocycline treatment reduced the iNOS expression and decreased the initial photoreceptor apoptosis, but did not provide long term ameliorative effect on the photoreceptor cell loss of rds mice.


CONCLUSIONS
NO played a major role in the initial photoreceptor apoptosis in rds mice. The migration of activated microglia to the ONL contributed to the subsequent photoreceptor cell death; minocycline treatment ameliorated the photoreceptor apoptosis in rds mice, and this protective effect was partly through iNOS-suppressive mechanism.
Yang
Li-ping
LP
Peking University Eye Center, Peking University Third Hospital, Peking University, Beijing, China.
Li
Ying
Y
Zhu
Xiu-an
XA
Tso
Mark O M
MO
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051379:Mice; D008817:Mice, Mutant Strains; D017628:Microglia / Q000187:drug effects; D008911:Minocycline / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020419:Photoreceptor Cells, Vertebrate; D012160:Retina / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D015854:Up-Regulation
D018925:Chemokines; D004791:Enzyme Inhibitors; D052247:Nitric Oxide Synthase Type II; D008911:Minocycline