Minocycline delays photoreceptor death in the rds mouse through a microglia-independent mechanism

Exp Eye Res. 2004 Jun;78(6):1077-84. doi: 10.1016/j.exer.2004.02.002.


Purpose: Minocycline, a semi-synthetic tetracycline antibiotic is reported to be neuroprotective in degenerative and ischaemic models of central nervous system disease, via mechanisms involving suppression of both cytotoxic microglial activity and caspase-dependent apoptosis. We have investigated the effect of minocycline treatment on a mouse model of retinitis pigmentosa, an inherited photoreceptor neurodegenerative disorder, and contrasted this with the effect of depleting retinal microglia using liposomal clodronate.

Methods: rds mice were treated intraperitoneally from the second postnatal day (P2) with either daily minocycline until P16, P18, P21, P24 and P27 or alternative day clodronate liposomes until P16. Immunohistochemical and immunofluorescent methods were applied for the detection of microglia (F4/80) and apoptosis (TUNEL and caspase 3 activation).

Results: Photoreceptor apoptosis was delayed by minocycline treatment but not, ultimately, prevented. Markedly reduced expression of activated caspase 3 was observed in photoreceptors at the early time point, corresponding with the reduced level of apoptosis. Delayed photoreceptor apoptosis due to minocycline treatment was associated with a 50% reduction in the numbers of microglia at early timepoints. Liposomal clodronate treatment also resulted in a marked reduction in the number of microglia (63% reduction in microglia), but in contrast to minocycline treatment, this had no effect on photoreceptor apoptosis.

Conclusions: Minocycline appears to delay photoreceptor apoptosis through a microglia-independent action. Although microglial cytotoxicity has been implicated during other models of neurodegeneration, microglia are unlikely to play such a role in this model of photoreceptor dystrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Clodronic Acid / administration & dosage
  • Clodronic Acid / pharmacology
  • In Situ Nick-End Labeling
  • Intermediate Filament Proteins / genetics
  • Liposomes
  • Membrane Glycoproteins / genetics
  • Mice
  • Mice, Knockout
  • Microglia / drug effects
  • Microglia / physiology*
  • Minocycline / therapeutic use*
  • Nerve Tissue Proteins / genetics
  • Neuroprotective Agents / therapeutic use*
  • Peripherins
  • Photoreceptor Cells, Vertebrate / drug effects*
  • Photoreceptor Cells, Vertebrate / pathology
  • Retinitis Pigmentosa / drug therapy*
  • Retinitis Pigmentosa / genetics
  • Retinitis Pigmentosa / pathology


  • Intermediate Filament Proteins
  • Liposomes
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Peripherins
  • Prph2 protein, mouse
  • Clodronic Acid
  • Minocycline