Retinal neuroprotection against ischemic injury mediated by intraocular gene transfer of pigment epithelium-derived factor

Hiroyasu Takita, Shin Yoneya, Peter L. Gehlbach, Elia J. Duh, Lisa L. Wei, Keisuke Mori

Research output: Contribution to journalArticle

Abstract

PURPOSE. To determine whether intraocular gene transfer of pigment epithelium-derived factor (PEDF) protects the retina from ischemia-reperfusion injury. METHODS. Four days before induction of pressure-induced ischemia, Lewis rats received intravitreous injection of 3 × 109 particles of an adenovirus vector expressing PEDF (AdPEDF.11) in one eye and 3 × 109 particles of an empty adenovirus vector (AdNull.11) in the contralateral eye. Seven days after reperfusion, eyes were enucleated and processed for morphometric analysis. Apoptotic cells stained by TdT-dUTP terminal nick-end labeling (TUNEL) in the retina were counted 12 hours after initiation of reperfusion. Retina levels of PEDF were measured by enzyme-linked immunosorbent assay. RESULTS. PEDF levels in retinal homogenates from eyes receiving AdPEDF.11 injection were well above the background levels in the untreated baseline and control eyes (P = 0.04). Retinal thickness was preserved in AdPEDF.11-treated eyes. Retinal cell density was significantly greater in the ganglion cell layer (GCL; P = 0.014), inner nuclear layer (INL; P = 0.008), and outer nuclear layer (ONL; P = 0.008) of AdPEDF.11-treated eyes compared with the corresponding layers in AdNull.11-treated eyes. AdNull.11-treated eyes also had significantly more TUNEL-positive cells in these layers than AdPEDF.11-treated eyes (P < 0.05). CONCLUSIONS. Adenoviral vector-mediated intraocular expression of PEDF significantly increases cell survival after ischemia-reperfusion injury of the retina. The protective effect may result from inhibition of ischemia-induced apoptosis. This study provides proof of concept for a gene transfer approach directed at interrupting programmed cell death induced by retinal ischemic insult.

Original languageEnglish (US)
Pages (from-to)4497-4504
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume44
Issue number10
DOIs
StatePublished - Oct 1 2003

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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