Rescue of Light Induced Photoreceptor Cell Death by Intraocular Gene Transfer of Pigment Epithelium-Derived Factor by Reducing Retinal Cell Apoptosis

Abstract

Abstract: : Purpose: To investigate whether intraocular gene transfer of pigment epithelium-derived factor (PEDF) prevents light-induced photoreceptor cell death. Methods: Lewis rats received intravitreous injection of 3x10⁹ particles of adenoviral vector expressing PEDF (AdPEDF.11) in one eye and 3x10⁹ particles of empty adenoviral vector (AdNull.11) in the contralateral eye. They were then dark-adapted for 3 days after which they were continuously exposed to fluorescent light (2500 lux) for 6, 24, 96 and 168 hours. Both eyes were then enucleated and processed for morphometric analysis. Cell death in the retina was examined using TUNEL staining with a propidium iodide counterstain. Results: Eyes with intravitreous injection of AdNull.11 showed numerous pyknotic photoreceptor cells and reduced cell density when compared to AdPEDF.11 injected eyes. The preservation of photoreceptor cell counts in eyes with AdPEDF.11 was statistically significant (p=0.015). There were many TUNEL-positive photoreceptor cells which correspond to pyknotic cells stained by propidium iodide in eyes with intravitreous injection of AdNull.11 but less in the retina with AdPEDF.11. Conclusions: Adenoviral vector-mediated intraocular expression of PEDF significantly increases photoreceptor cell survival following excessive light exposure. The neuroprotection may result from inhibition of light-induced apoptotic processes. This study provides proof of concept for a gene transfer approach to modulating retinal cell death resulting from photo-oxidative damage and may suggest that gene transfer of PEDF is broadly applicable to modulating apoptosis in the retina.

Keywords: neuroprotection • apoptosis/cell death • radiation damage: light/UV