Differential expression of anti-angiogenic factors and guidance genes in the developing macula

• Published in: Molecular vision 2009-01, Vol.15, p.45-59
• Main Authors: Kozulin, Peter, Natoli, Riccardo, O'Brien, Keely M Bumsted, Madigan, Michele C, Provis, Jan M
• Format: Article
• Language: English
• Subjects: Adult; Angiogenesis Inhibitors - genetics; Angiogenesis Inhibitors - metabolism; Animals; Axons - metabolism; Eye Proteins - drug effects; Eye Proteins - metabolism; Fetus - metabolism; Gene Expression Profiling; Gene Expression Regulation, Developmental; Humans; In Situ Hybridization; Macaca; Macula Lutea - embryology; Macula Lutea - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Multigene Family; Nerve Growth Factors - drug effects; Nerve Growth Factors - metabolism; Oligonucleotide Array Sequence Analysis; Primates; Quality Control; RNA, Messenger - genetics; RNA, Messenger - metabolism; Serpins - drug effects; Serpins - metabolism
• ISSN: 1090-0535; 1090-0535

The primate retina contains a specialized, cone-rich macula, which mediates high acuity and color vision. The spatial resolution provided by the neural retina at the macula is optimized by stereotyped retinal blood vessel and ganglion cell axon patterning, which radiate away from the macula and reduce shadowing of macular photoreceptors. However, the genes that mediate these specializations, and the reasons for the vulnerability of the macula to degenerative disease, remain obscure. The aim of this study was to identify novel genes that may influence retinal vascular patterning and definition of the foveal avascular area. We used RNA from human fetal retinas at 19-20 weeks of gestation (WG; n=4) to measure differential gene expression in the macula, a region nasal to disc (nasal) and in the surrounding retina (surround) by hybridization to 12 GeneChip microarrays (HG-U133 Plus 2.0). The raw data was subjected to quality control assessment and preprocessing, using GC-RMA. We then used ANOVA analysis (Partek) Genomic Suite 6.3) and clustering (DAVID website) to identify the most highly represented genes clustered according to "biological process." The neural retina is fully differentiated at the macula at 19-20 WG, while neuronal progenitor cells are present throughout the rest of the retina. We therefore excluded genes associated with the cell cycle, and markers of differentiated neurons, from further analyses. Significantly regulated genes (p