Minocycline delayed photoreceptor death in the rds mice throughiNOS-dependent mechanism

[摘要] Purpose: To elucidate the role of activated microglia and nitricoxide (NO) in photoreceptor apoptosis in rds mice, and to investigatethe effect of minocycline treatment on rds mice.Methods: Photoreceptor apoptosis in rds mice was detected byterminal dUTP transferase nick end labeling (TUNEL). Retinal microglialcells were identified by CD11b antibody. The mRNA expression ofinducible nitric oxide synthase (iNOS) and chemokines were examined byreverse transcription polymerase chain reaction (RT-PCR) assay. Theprotein expression of iNOS was examined by immunohistochemistry andWestern blotting analysis. The rds mice were treated intra-peritoneallyfrom 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 wasup-regulated. Minocycline treatment reduced the iNOS expression anddecreased the initial photoreceptor apoptosis, but did not provide longterm ameliorative effect on the photoreceptor cell loss of rds mice.Conclusions: NO played a major role in the initial photoreceptorapoptosis in rds mice. The migration of activated microglia to the ONLcontributed to the subsequent photoreceptor cell death; minocyclinetreatment ameliorated the photoreceptor apoptosis in rds mice, and thisprotective effect was partly through iNOS-suppressive mechanism.

[学科分类] 生物化学/生物物理