RNA-Seq analysis in giant pandas reveals the differential expression of multiple genes involved in cataract formation

Abstract

Background The giant panda (Ailuropoda melanoleuca) is an endangered mammalian species native to China. Fewer than 2500 giant pandas are known to exist, many of which are bred in captivity as a means to preserve and repopulate the species. Like other captive mammals, giant pandas acquire age-related cataracts, reducing their quality of life. Recent comparative genome-wide methylation analysis revealed 110 differentially methylated genes associated with cataract formation including six also associated with the formation of age-related cataracts in humans. Results To investigate the pathological pathway in greater detail, here we used RNA-Seq analysis to investigate the differential expression profiles of genes in three giant pandas with cataracts and three healthy controls. We identified more than 700 differentially expressed genes, 29 of which were selected for further analysis based on their low q-value. We found that many of the genes encoded regulatory and signaling proteins associated with the control of cell growth, migration, differentiation and apoptosis, supporting previous research indicating a key role for apoptosis in cataract formation. Conclusion The identification of genes involved in the formation of age-related cataracts could facilitate the development of predictive markers, preventative measures and even new therapies to improve the life of captive animals.

Comparative proteomics in captive giant pandas to identify proteins involved in age-related cataract formation

“…The development of age-related cataracts is mainly promoted by environmental factors that cause oxidative damage to DNA and proteins 5 – 7 , 9 . This triggers changes in DNA methylation and gene expression, and in previous studies we and others have identified target genes involved in apoptosis, DNA repair and oxidative stress responses that may represent an attempt to counter or reverse the damage that occurs during cataract formation 17 , 18 , 24 – 26 .…”

“…Epigenetic modifications such as DNA methylation can directly affect transcription, and we have previously reported correlations between the methylated loci detected in panda cataracts and the modulation of gene expression in affected vs unaffected individuals 17 , 18 . However, the regulation of gene expression at the level of protein synthesis and turnover means that transcript and protein levels often do not correlate directly, and this is particularly relevant in the lens where the proteome is known to have a very slow turnover compared to non-lens tissues in the eye, suggesting that serum markers of cataract formation may not track closely with mRNA levels 27 .…”

“…Previous studies in several mammalian species have investigated the regulation of transcription during the development of cataracts as well as differences in DNA methylation and/or RNA profiles between normal and affected individuals 14 – 16 . In our previous work, we identified 110 candidate genes that are differentially methylated in giant pandas with and without cataracts (including six genes associated with age-related cataracts in humans) 17 as well as more than 700 differentially expressed transcripts 18 . However, the vast majority of gene products that act as effectors during cataract formation are proteins rather than RNA molecules, and changes at the RNA level do not always correlate directly with changes at the protein level.…”