A zebrafish retinal graded photochemical stress model.

Abstract

INTRODUCTION: In order to develop a model for investigating the genes that contribute to retinal degeneration, we examined the early graded photochemical stress response in the adult zebrafish (Danio rerio) retina and investigated the role of an NMDA inhibitor, thiokynurenate. METHODS: Following intravitreal injection of rose bengal (6 or 12 mg/mL), light (37x10(3) or 83x10(3) lx) was directed onto the central retina with and without 400 nM thiokynurenate. Histologic and electron microscopic analysis was performed at 2 and 4 h and gene expression analysis was carried out at 2, 4 and 6 h. RESULTS: Light and electron microscopy demonstrated a graded photochemical response in photoreceptor, nuclear, and ganglion cell layer thickness. Increased vacuolation of the inner plexiform layer was also observed. The inhibitor produced a distinct lesion pattern. Cellular stress genes were elevated in low and high lesions, while some homeobox gene expression was reduced with thiokynurenate. DISCUSSION: The phenotypic and genetic changes observed from this model can serve as a basis for understanding the pathology of retinal oxidative and cellular stress. These changes may aid our understanding of aging and macular degeneration.