Disease gene candidates revealed by expression profiling of retinal ganglion cell development
- PMID: 17687037
- PMCID: PMC2885852
- DOI: 10.1523/JNEUROSCI.4488-06.2007
Disease gene candidates revealed by expression profiling of retinal ganglion cell development
Abstract
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.
Figures
![Figure 1.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6672928/bin/zns0310736430001.gif)
![Figure 2.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6672928/bin/zns0310736430002.gif)
![Figure 3.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6672928/bin/zns0310736430003.gif)
![Figure 4.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6672928/bin/zns0310736430004.gif)
![Figure 5.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6672928/bin/zns0310736430005.gif)
![Figure 6.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6672928/bin/zns0310736430006.gif)
![Figure 7.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6672928/bin/zns0310736430007.gif)
Similar articles
-
Microarray analysis of gene expression in adult retinal ganglion cells.FEBS Lett. 2006 Jan 9;580(1):331-5. doi: 10.1016/j.febslet.2005.12.017. Epub 2005 Dec 19. FEBS Lett. 2006. PMID: 16376886
-
Gene expression profiling of purified rat retinal ganglion cells.Invest Ophthalmol Vis Sci. 2004 Aug;45(8):2503-13. doi: 10.1167/iovs.03-1391. Invest Ophthalmol Vis Sci. 2004. PMID: 15277470
-
Changes in gene expression in experimental glaucoma and optic nerve transection: the equilibrium between protective and detrimental mechanisms.Invest Ophthalmol Vis Sci. 2007 Dec;48(12):5539-48. doi: 10.1167/iovs.07-0542. Invest Ophthalmol Vis Sci. 2007. PMID: 18055803
-
Tools and resources for analyzing gene expression changes in glaucomatous neurodegeneration.Exp Eye Res. 2015 Dec;141:99-110. doi: 10.1016/j.exer.2015.05.009. Epub 2015 May 19. Exp Eye Res. 2015. PMID: 25999234 Free PMC article. Review.
-
Research progress on human genes involved in the pathogenesis of glaucoma (Review).Mol Med Rep. 2018 Jul;18(1):656-674. doi: 10.3892/mmr.2018.9071. Epub 2018 May 23. Mol Med Rep. 2018. PMID: 29845210 Free PMC article. Review.
Cited by
-
Upregulation of developmentally-downregulated miR-1247-5p promotes neuroprotection and axon regeneration in vivo.Neurosci Lett. 2024 Feb 16;823:137662. doi: 10.1016/j.neulet.2024.137662. Epub 2024 Jan 28. Neurosci Lett. 2024. PMID: 38286398
-
Purification of Retinal Ganglion Cells from Differentiation Through Adult via Immunopanning and Low-Pressure Flow Cytometry.Methods Mol Biol. 2023;2708:11-24. doi: 10.1007/978-1-0716-3409-7_2. Methods Mol Biol. 2023. PMID: 37558955
-
Purification of retinal ganglion cells using low-pressure flow cytometry.Front Mol Neurosci. 2023 Jul 20;16:1149024. doi: 10.3389/fnmol.2023.1149024. eCollection 2023. Front Mol Neurosci. 2023. PMID: 37547921 Free PMC article.
-
Moving CNS axon growth and regeneration research into human model systems.Front Neurosci. 2023 Jun 22;17:1198041. doi: 10.3389/fnins.2023.1198041. eCollection 2023. Front Neurosci. 2023. PMID: 37425013 Free PMC article. Review.
-
Elk-1 regulates retinal ganglion cell axon regeneration after injury.Sci Rep. 2022 Oct 19;12(1):17446. doi: 10.1038/s41598-022-21767-3. Sci Rep. 2022. PMID: 36261683 Free PMC article.
References
-
- Ahn JH, Kang HH, Kim YJ, Chung JW. Anti-apoptotic role of retinoic acid in the inner ear of noise-exposed mice. Biochem Biophys Res Commun. 2005;335:485–490. - PubMed
-
- Ang HL, Deltour L, Zgombic-Knight M, Wagner MA, Duester G. Expression patterns of class I and class IV alcohol dehydrogenase genes in developing epithelia suggest a role for alcohol dehydrogenase in local retinoic acid synthesis. Alcohol Clin Exp Res. 1996a;20:1050–1064. - PubMed
-
- Ang HL, Deltour L, Hayamizu TF, Zgombic-Knight M, Duester G. Retinoic acid synthesis in mouse embryos during gastrulation and craniofacial development linked to class IV alcohol dehydrogenase gene expression. J Biol Chem. 1996b;271:9526–9534. - PubMed
-
- Arlotta P, Molyneaux BJ, Chen J, Inoue J, Kominami R, Macklis JD. Neuronal subtype-specific genes that control corticospinal motor neuron development in vivo. Neuron. 2005;45:207–221. - PubMed
-
- Barres BA, Silverstein BE, Corey DP, Chun LL. Immunological, morphological, and electrophysiological variation among retinal ganglion cells purified by panning. Neuron. 1988;1:791–803. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases