Altered miRNA expression in canine retinas during normal development and in models of retinal degeneration

BMC Genomics

Gustavo D Aguirre¹  William A Beltran¹  Karina E Guziewicz¹  Sem Genini¹ 

[1] Department of Clinical Studies-Philadelphia, Section of Ophthalmology, School of Veterinary Medicine, University of Pennsylvania, 3900 Delancey Street, 19104 Philadelphia, PA, USA

关键词: xlpra2;    rcd1;    qRT-PCR;    prcd;    miRNA expression profiles;    Microarray;    Inherited retinal disorders;    erd;    Canine models;    Apoptomirs;   

Others  :  1217824
DOI  :  10.1186/1471-2164-15-172

 received in 2013-12-07, accepted in 2014-02-17,  发布年份 2014

【 摘 要 】

Background

Although more than 246 loci/genes are associated with inherited retinal diseases, the mechanistic events that link genetic mutations to photoreceptor cell death are poorly understood. miRNAs play a relevant role during retinal development and disease. Thus, as a first step in characterizing miRNA involvement during disease expression and progression, we examined miRNAs expression changes in normal retinal development and in four canine models of retinal degenerative disease.

Results

The initial microarray analysis showed that 50 miRNAs were differentially expressed (DE) early (3 vs. 7 wks) in normal retina development, while only 2 were DE between 7 and 16 wks, when the dog retina is fully mature. miRNA expression profiles were similar between dogs affected with xlpra2, an early-onset retinal disease caused by a microdeletion in RPGRORF15, and normal dogs early in development (3 wks) and at the peak of photoreceptor death (7 wks), when only 2 miRNAs were DE. However, the expression varied much more markedly during the chronic cell death stage at 16 wks (118 up-/55 down-regulated miRNAs). Functional analyses indicated that these DE miRNAs are associated with an increased inflammatory response, as well as cell death/survival. qRT-PCR of selected apoptosis-related miRNAs (“apoptomirs”) confirmed the microarray results in xlpra2, and extended the analysis to the early-onset retinal diseases rcd1 (PDE6B-mutation) and erd (STK38L-mutation), as well as the slowly progressing prcd (PRCD-mutation). The results showed up-regulation of anti-apoptotic (miR-9, -19a, -20, -21, -29b, -146a, -155, -221) and down-regulation of pro-apoptotic (miR-122, -129) apoptomirs in the early-onset diseases and, with few exceptions, also in the prcd-mutants.

Conclusions

Our results suggest that apoptomirs might be expressed by diseased retinas in an attempt to counteract the degenerative process. The pattern of expression in diseased retinas mirrored the morphology and cell death kinetics previously described for these diseases. This study suggests that common miRNA regulatory mechanisms may be involved in retinal degeneration processes and provides attractive opportunities for the development of novel miRNA-based therapies to delay the progression of the degenerative process.

【 授权许可】

   
2014 Genini et al.; licensee BioMed Central Ltd.

【 图 表 】

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