Developmental death of photoreceptors in the C57BL/6J mouse: association with retinal function and self-protection.
We have investigated the relationship between cell death among photoreceptors and the expression of function- and stress-related proteins during the development of the retina of the C57BL/6J mouse. Retinas from mice aged P(postnatal day)4 to P63 (adult) were examined for cell death using the TUNEL technique, and for the expression of basic fibroblast growth factor (bFGF), cytochrome oxidase (CO), rod opsin and glial fibrillary acidic protein (GFAP), using immunocytochemistry. At P4, cell death is most prominent in the inner layers of retina, declining to near-zero levels by P16. Cell death among photoreceptors occurs in a discrete wave commencing at approximately P12 and remaining elevated into the 4th postnatal week, beginning, peaking and declining later than in inner retina. The onset of photoreceptor death correlates with the expression of function-related molecules, such as CO and opsin. The decline in photoreceptor death correlates with the expression of the protective factor bFGF in photoreceptors. At the anterior edge of the retina photoreceptor death and the expression of bFGF are accelerated, and the expression of bFGF and GFAP is upregulated, by an edge-specific stress. We conclude that in the mouse photoreceptors undergo a wave of death which culls the neonatal population to adult levels. The onset of photoreceptor death is related to the acceleration of photoreceptor metabolism and function between P12 and P20. The decline of photoreceptor death to the very low levels found in the adult may be mediated by the upregulation of protective factors such as bFGF. Photoreceptor death and the expression of bFGF and GFAP at the edge of the retina are regulated by a still-unidentified, edge-specific stress, from as early as P16.
Mervin
Kyle
K
Department of Anatomy and Histology, NSW Retinal Dystrophy Research Centre, University of Sydney, Sydney 2006, NSW, Australia. kyle@anatomy.usyd.edu.au
Stone
Jonathan
J
D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D016923:Cell Death; D003576:Electron Transport Complex IV / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D012160:Retina / Q000254:growth & development / Q000378:metabolism / Q000502:physiology; D017299:Rod Opsins / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; D017299:Rod Opsins; D016222:Fibroblast Growth Factor 2; D003576:Electron Transport Complex IV; D011493:Protein Kinase C