Differential gene expression patterns of the developing and adult mouse cornea compared to the lens and tendon

Abstract

The cornea continues to mature after birth to develop a fully functional, refractive and protective barrier tissue. Here we investigated the complex biological events underlying this process by profiling global genome-wide gene expression patterns of the immature postnatal day 10 and seven week-old adult mouse cornea. The lens and tendon were included in the study to increase the specificity of genes identified as up regulated in the corneal samples. Notable similarities in gene expression between the cornea and the tendon were in the mesenchymal extracellular matrix collagen (types I, III, V, VI) and proteoglycan (lumican, decorin and biglycan) genes. Expression similarities in the cornea and lens were limited to certain epithelial genes and the crystallins. Approximately 76 genes were over expressed in the cornea samples that showed basal expression levels in the lens and tendon. Thirty-two of these were novel with no known functions in the cornea. These include genes with a potential role in protection against oxidative stress (Dhcr24, Cdo1, Akr1b7, Prdx6), inflammation (Ltb4dh, Wdr1), ion-transport (Pdzk1ip1, Slc12a2, Slc25a17) and transcription (Zfp36l3, Pdzk1ip1). Direct comparison of the cornea of two ages showed selective up regulation of 50 and 12 genes in the P10 and adult cornea, respectively. Of the up regulated P10 genes several encode extracellular matrix collagens and proteoglycans that are stable components of the adult cornea and their high transcriptional activity at P10 indicate a period of active corneal growth and matrix deposition in the young cornea. Much less is known about the genes selectively over expressed in the adult cornea; some relate to immune response and innervation (Npy), and possibly to electron transport (Cyp24a1, Cyp2f2) and others of yet unknown functions in the cornea (Rgs10, Psmb8, Xlr4)). This study detected expression of genes with known functions in the cornea, providing additional validation of the microarray experiments. Importantly, it identified several novel genes whose functions have not been investigated in the cornea.

Age-related changes in regulator of G-protein signaling (RGS)-10 expression in peripheral and central immune cells may influence the risk for age-related degeneration

“…The role of RGS10 in human disease has not been thoroughly assessed but age-related maculopathy pathology demonstrates significant microglial activation (Buschini, et al, 2011). Interestingly, RGS10 expression in the mouse cornea increases with age but this change in expression has not be contextualized in human disease (Wu, et al, 2008). Extended immunophenotyping studies of human peripheral blood and post-mortem brains are warranted to elucidate whether altered expression of RGS10 in immune cells is detectable in age-related diseases characterized by inflammation such as age-related maculopathy and neurodegenerative diseases like Parkinson’s disease.…”

The Ets Transcription Factor EHF as a Regulator of Cornea Epithelial Cell Identity

“…Another study compared cornea stroma mRNA expression from P10 and adult mice with that of cultured keratocytes, fibroblasts, and myofibroblasts, revealing a role for the stroma in maintenance of transparency as well as in barrier protection during times of infection or injury (10). A third study compared whole cornea mRNA expression in P10 and 7-week-old mice with that of lens and tendon, defining cornea-enriched genes compared with the lens and tendon (9). The comprehensive picture of cornea gene expression in our study provides new insights into both cornea development and aging, helps define the transition point between development and adulthood, and identifies new pathways and genes involved in development and aging.…”

Overview of the Cornea

“…In mice, microarray analysis of the expression of 8666 genes between postnatal day 10 and days 49-56 revealed 442 genes with distinct levels of expression between the two time points. 50 MicroRNA (miRNA) function is essential for epithelial development, and targeted deletion of a ribonuclease necessary for miRNA function, Dicer, results in poorly stratified corneal epithelium and microphthalmia. 51 In human-induced pluripotent stem cells, miR-450b-5p serves as a switch for Pax6, inhibiting Pax6 expression and directing corneal epithelial fate; miR-184 is expressed in the corneal epithelium, and knockdown results in decreased Pax6 expression.…”