Activated microglia in human retinitis pigmentosa, late-onset retinal degeneration, and age-related macular degeneration

Nisha Gupta, Kimberly E. Brown, Ann H. Milam

Research output: Contribution to journalArticle

336 Scopus citations

Abstract

Many gaps exist in our knowledge of human retinal microglia in health and disease. We address the hypothesis that primary death of rod photoreceptors leads to activation of resident microglia in human retinas with retinitis pigmentosa (RP), late-onset retinal degeneration (L-ORD), or age-related macular degeneration (AMD). Regions of ongoing photoreceptor cell death were studied by immunocytochemistry with microglia- and other retinal cell-specific markers. In normal human retinas, quiescent microglia were small, stellate cells associated with inner retinal blood vessels. In retinas with RP, L-ORD, or AMD, numerous activated microglia were present in the outer nuclear layer in regions of ongoing rod cell death. These microglia were enlarged, amoeboid cells that contained rhodopsin-positive cytoplasmic inclusions. We conclude that activated microglia migrate to the outer nuclear layer and remove rod cell debris. In other central nervous system diseases such as stroke, activated microglia phagocytose debris from the primary injury and also secrete molecules that kill nearby normal neurons. By analogy with these diseases, we suggest that microglia activated by primary rod cell death may kill adjacent photoreceptors. Activated microglia may be a missing link in understanding why initial rod cell death in the human diseases RP, L-ORD, and AMD leads to death of the cones that are critical for high acuity daytime vision.

Original languageEnglish (US)
Pages (from-to)463-471
Number of pages9
JournalExperimental Eye Research
Volume76
Issue number4
DOIs
StatePublished - Apr 1 2003

Keywords

  • Age-related macular degeneration
  • Cones
  • Human retinal diseases
  • Immunocytochemistry
  • Late-onset retinal degeneration
  • Microglia
  • Retinitis pigmentosa
  • Rods

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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