Disease gene candidates revealed by expression profiling of retinal ganglion cell development.
To what extent do postmitotic neurons regulate gene expression during development or after injury? We took advantage of our ability to highly purify retinal ganglion cells (RGCs) to profile their pattern of gene expression at 13 ages from embryonic day 17 through postnatal day 21. We found that a large proportion of RGC genes are regulated dramatically throughout their postmitotic development, although the genes regulated through development in vivo generally are not regulated similarly by RGCs allowed to age in vitro. Interestingly, we found that genes regulated by developing RGCs are not generally correlated with genes regulated in RGCs stimulated to regenerate their axons. We unexpectedly found three genes associated with glaucoma, optineurin, cochlin, and CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1), previously thought to be primarily expressed in the trabecular meshwork, which are highly expressed by RGCs and regulated through their development. We also identified several other RGC genes that are encoded by loci linked to glaucoma. The expression of glaucoma-linked genes by RGCs suggests that, at least in some cases, RGCs may be directly involved in glaucoma pathogenesis rather than indirectly involved in response to increased intraocular pressure. Consistent with this hypothesis, we found that CYP1B1 overexpression potentiates RGC survival.
Wang
Jack T
JT
Department of Neurobiology, Stanford University School of Medicine, Stanford, California 94305, USA.
Kunzevitzky
Noelia J
NJ
Dugas
Jason C
JC
Cameron
Meghan
M
Barres
Ben A
BA
Goldberg
Jeffrey L
JL
D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000502:physiology; D005128:Eye Diseases / Q000235:genetics* / Q000378:metabolism; D005136:Eye Proteins / Q000096:biosynthesis* / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005901:Glaucoma / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000502:physiology*
D005136:Eye Proteins