Purchase this article with an account.
Svetlana V. Kiosseva, Lily L. Wong, Xiaohong Zhou, James F. McGinnis; Genome-Wide Expression Profiling in the Retina of Vldlr Knockout Mouse. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1142.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To identify candidate genes and pathways that are involved in the pathophisiology of Age related Macular Degeneration (AMD) by microarray analysis of the retinas of Very low density lipoprotein receptor (Vldlr-/-) knockout mouse, an animal model for a form of AMD called Retinal Angiomatous Proliferation (RAP). We focused on characterization of the early events of retinal defects at postnatal day (P)14 when subretinal neovascularization begins and in the newly matured (P28) retina.
Labeled and amplified cRNAs from wild type (WT) and Vldlr-/- mice on a C57/BL6J background were hybridized to Illumina’s Sentrix Mouse-6 Expression BeadChip arrays containing~47,000 transcripts. Gene expression from scanned images was quantified, analyzed and shown as fold change when comparing Vldlr-/- to WT mouse retinas. Genes that changed by 1.8 fold and pFDR<0.05 were subsequently analyzed. Ingenuity Pathway Analysis (IPA) was used to search for biological processes, pathways and networks. The expression of several genes with notable fold change values was confirmed by qRT-PCR and differential protein expression by Western blots.
Two hundred eleven genes (P14) and 229 genes (P28) were differentially expressed in Vldlr-/- retina. Sixty six genes (P14) and 80 genes (P28) were up-regulated, and 145 (P14) and 140 (P28) genes were down-regulated, respectively. The top up-regulated genes were Serpina3n and Gdpd3 at P14, Serpina3n and Edn2 at P28, and down-regulated genes were Guca1b and Tomm22 at P14, Tomm22 and Mns1 at P28. Fourteen up-regulated genes were common to two point times including Gdpd3, Rgs5, Serpina3n, Crym, Tomm22, and 40 common genes were down-regulated (Guca1b, Pde6c, Myo7, Picalm, Ccl21b). The differentially expressed genes included those involved in developmental and genetic disorders, ophthalmic, neurological and metabolic diseases. The top canonical pathways for up-regulated genes were intrinsic prothrombin activation and cell cycle checkpoint control (P14), acute phase response and oncostatin M signaling (P28), while the phototransduction pathway was the top canonical pathway for the down-regulated genes.
This study demonstrates novel genome-wide transcriptional profiling data of retinal development in a mouse model of AMD and further provide new insights into the molecular pathways and networks that can be targets for new therapeutics.
This PDF is available to Subscribers Only