Photoreceptor synapses degenerate early in experimental choroidal neovascularization

Alejandro Caicedo, Diego Gabriel Espinosa Heidmann, Duco Hamasaki, Yolanda Piña, Scott W. Cousins

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Severe visual loss in patients with age-related macular degeneration is associated with the development of choroidal neovascularization (CNV). The pathogenic mechanisms for CNV formation have been extensively investigated, but remarkably little research has addressed the mechanisms for dysfunction of the retina in CNV. Using laser-induced CNV in mice, we evaluated the mechanisms of retinal dysfunction. At 3 days, 1 week, 2 weeks, and 4 weeks after laser application, retinas under experimental CNV were characterized physiologically (ERG recordings, synaptic uptake of the exocytotic marker FM1-43, and light-induced translocation of transducin), histologically, and immunohistochemically. ERG amplitudes were reduced by 20% at 1 week after CNV. Depolarization-induced FM1-43 uptake in photoreceptor synapses was selectively reduced by 45% at 1 week after CNV. Although photoreceptor outer segments were shortened by 36%, light adaptation as measured by transducin translocation was mostly preserved. Early in CNV (3 days to 1 week), Muller cells demonstrated induction of c-fos and pERK expression. Also, the density of macrophage-like, F4/80 immunoreactive cells increased ∼3-fold. Minimal photoreceptor death occurred during the first week, and was variable thereafter. At later times in CNV formation (≥2 weeks), expression of photoreceptor synaptic markers was reduced in the outer plexiform layer, indicating loss of photoreceptor synaptic terminals. ERG amplitudes, synaptic uptake of FM1-43, and the induction of c-fos and pERK in Muller cells were altered within 1 week of experimental CNV, suggesting that during CNV formation, deficits in retinal function, in particular photoreceptor synaptic function, precede degeneration of photoreceptor terminals and photoreceptor cell death.

Original languageEnglish (US)
Pages (from-to)263-277
Number of pages15
JournalJournal of Comparative Neurology
Volume483
Issue number3
DOIs
StatePublished - Mar 14 2005

Fingerprint

Choroidal Neovascularization
Synapses
Transducin
Ependymoglial Cells
Retina
Lasers
Ocular Adaptation
Photoreceptor Cells
Presynaptic Terminals
Macular Degeneration
Cell Death
Macrophages

Keywords

  • Age-related macular degeneration
  • Electroretinogram
  • FM1-43
  • Macrophages
  • Muller glial cell

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Photoreceptor synapses degenerate early in experimental choroidal neovascularization. / Caicedo, Alejandro; Espinosa Heidmann, Diego Gabriel; Hamasaki, Duco; Piña, Yolanda; Cousins, Scott W.

In: Journal of Comparative Neurology, Vol. 483, No. 3, 14.03.2005, p. 263-277.

Research output: Contribution to journalArticle

Caicedo, Alejandro ; Espinosa Heidmann, Diego Gabriel ; Hamasaki, Duco ; Piña, Yolanda ; Cousins, Scott W. / Photoreceptor synapses degenerate early in experimental choroidal neovascularization. In: Journal of Comparative Neurology. 2005 ; Vol. 483, No. 3. pp. 263-277.
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