Abstract
Purpose: :
The purpose of this work was: i) to compare same tissue-type transcript profiles from the eyes of the same donor; ii) to identify tissue-specific genes; iii) and to identify novel neuro-endocrine axis networks.
Methods: :
Six pairs of whole globes were obtained (NDRI) from deceased donors within 24h after death, and tissues (cornea, TM, iris, lens, CB, retina, RPE, sclera) from each individual eye were excised and collected separately. Total RNA was isolated from each tissue with TRIzol, purified with Qiagen RNeasy and processed on Illumina BeadChip array platform. The data analysis was performed with ArrayStar (Lasergene) software. Gene Ontology and Pathway analysis were performed by The Database for Annotation, Visualization and Integrated Discovery (DAVID).
Results: :
Transcript profiles of same tissue-type, from the eyes of the same donor, revealed small or no significant differences. However, they showed significant inter-individual variability in the relative gene expression abundance. Microarray data analysis also revealed the identification of cluster of genes highly restricted in a tissue-specific manner, suggesting unique functions. In particular, the expression of genes encoding components of the hypothalamic-pituitary-thyroid axis, including TRH and PRL in the retina, and PRLR in the iris, suggesting potential neuro-endocrine communication systems between these tissues. The expression of type-2 and type-3 deiodinase enzymes by ocular tissues of the anterior segment also suggested uptake and metabolism of the thyroid hormone by the ciliary body. On the other hand, the expression of gonadotropin-releasing hormone (GnRH) in the lens and GnRH receptor (GnRHR1) in the retina, suggested the potential synthesis and secretion of follicle-stimulating hormone (FSH) and/or luteinizing hormone (LH) within the eye, since the luteinizing hormone/choriogonadotropin receptor (LHCGR) is expressed in the iris.
Conclusions: :
We have generated an atlas with a comprehensive survey of human gene expression profiles in ocular tissues from single eyes, and identified clusters of genes that are restricted to each tissue. The microarray data analysis revealed the identification of components of a hypothalamic-pituitary-thyroid axis in the eye suggesting the presence of physiological processes involved in the metabolic control of thyroid hormones and neuro-endocrine signaling.
Keywords: gene/expression • gene microarray • neuropeptides