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Regulation of retinal ganglion cell gene expression by bHLH transcription factors in the developing and ischemic retinas
Author(s) -
MATTER JM,
CHIODINI F,
DELAFOSSE L,
MATTERSADZINSKI L,
POURNARAS CJ
Publication year - 2009
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2009.2141.x
Subject(s) - biology , neuroprotection , microbiology and biotechnology , retina , retinal ganglion cell , anaerobic glycolysis , transcription factor , neuroscience , glycolysis , gene , genetics , endocrinology , metabolism
Purpose The loss of retinal ganglion cells (RGC) in the glaucomatous retina exhibits similarities to the pattern of neuronal degeneration detected after experimental ischemia. However, a short episode of retinal ischemia does not provoke damage but rather triggers an endogenous form of neuroprotection. HIFs are bHLH proteins that regulate hypoxic response in ischemic retinas and they are involved in neuroprotection. Hypoxic environments also occur in the developing embryo and create specific niches controlling cell differentiation. Genetic analyses of HIF functions have revealed the importance of oxygen as a key regulator of ontogeny. We have compared the transcriptomes of RGCs in ischemic versus developing retinas. Methods Genome‐wide screens were conducted to identify genes which are expressed in newborn RGCs and growing optic nerve axons and which are up‐ or down‐regulated after venal occlusion by photodynamic thrombosis in the rat retinas. Results Atoh7 is a bHLH protein which is central to the transcriptional network regulating the production of RGCs. Among the targets of Atoh7 there are genes involved in the general metabolism and energy supply – e.g., alpha‐enolase (ENO1), glucose‐6 ‐phosphate isomerase (GPI). These glycolytic enzymes are also targets of HIFs and they are upregulated during hypoxia. To investigate the linkage of glycolysis and mitochondrial activity in RGCs, we monitored by confocal time‐lapse imaging the dynamic distribution of mitochondria in the cell bodies and axons of RGCs that express HIF/Atoh7 targets in developing and ischemic retinas. Conclusion Some gene expression programs involved in differentiating RGCs might be reinitiated in neuroprotection.