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S. Genini, B. Zangerl, G. M. Acland, W. Beltran, G. D. Aguirre; Disease Associated Changes in Gene Expression in RPGRORF15 Frameshift Mutant Retina. Invest. Ophthalmol. Vis. Sci. 2009;50(13):493.
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© ARVO (1962-2015); The Authors (2016-present)
To identify genes and molecular mechanisms associated with disease progression in dogs affected with XLPRA2, a canine model of early-onset XLRP caused by a microdeletion in RPGR exon ORF15.
Expression profiles of diseased and normal dog retinas at 7 and 16 weeks of age were compared using a canine retinal custom cDNA microarray containing ~4,500 transcripts. Data normalization and filtering were performed with GeneSpring, statistical analysis with SAM (FDR <10%).
At 7 and 16 weeks, respectively, 58 and 18 transcripts were differentially expressed (DE). All 76 transcripts were down-regulated in mutant retinas compared to normals; none of the transcripts was DE at both ages. DE genes included PAX6 (7 weeks) and CRX (16 weeks), which are relevant in brain and central nervous system development, and, like SAG (DE at 16 weeks), are necessary for a correct visual function. Furthermore, genes directly or indirectly involved in apoptotic processes were altered at 7 weeks (CAMK2G, NTRK2, PRKCB1, RALA, RBBP6, RNF41, SEPT5, SMYD3, SPP1 and TUBB2C). SEPT5 and TUBB2C are also related to mitochondrial functions as are other DE genes at 7 weeks (ELOVL6, GLOD4, NDUFS4 and REEP1) and 16 weeks (SLC25A5 and TARS2) of age.
A list of down-regulated genes in RPGRORF15 mutant retinas at different ages is reported. The results indicate that at 7 weeks (peak of cell death) a combination of non-classical anti- and pro-apoptotic genes appears to be involved, whereas at 7 and 16 weeks (reactive repair phase), expression of mitochondria related genes indicates they may play a relevant role in this phase of disease. Real-time PCR of selected genes is currently in progress to validate DE genes, and to evaluate crucial genes known to regulate progression of photoreceptor degeneration in other similar retinal diseases.
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