A zebrafish retinal graded photochemical stress model.
BACKGROUND
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.


CONCLUSIONS
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.
Eichenbaum
Joseph W
JW
Department of Ophthalmology, Mount Sinai School of Medicine, USA. Joseph.Eichenbaum@mssm.edu
Cinaroglu
Ayca
A
Eichenbaum
Kenneth D
KD
Sadler
Kirsten C
KC
D000818:Animals; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D007267:Injections; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008027:Light / Q000009:adverse effects; D008854:Microscopy, Electron; D018384:Oxidative Stress; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D012395:Rose Bengal; D014822:Vitreous Body; D015027:Zebrafish
D016194:Receptors, N-Methyl-D-Aspartate; C076191:thiokynurenate; D012395:Rose Bengal; D007736:Kynurenic Acid