Megan Ulmer Carnes1, R Rand Allingham2, Allison Ashley-Koch3, Michael A Hauser4. 1. Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. Electronic address: megan.carnes@nih.gov. 2. Department of Ophthalmology, Duke University School of Medicine, Durham, NC, USA. 3. Department of Medicine, Duke University Medical Center, Durham, NC, USA; Center for Human Disease Modeling, Duke University Medical Center, Durham, NC, USA. 4. Department of Ophthalmology, Duke University School of Medicine, Durham, NC, USA; Department of Medicine, Duke University Medical Center, Durham, NC, USA; Duke Molecular Physiology Institute, Durham, NC, USA.
Abstract
PURPOSE: To characterize the transcriptional landscape of human adult and fetal trabecular meshwork (TM), cornea, and ciliary body (CB) tissues, and to evaluate the expression level of candidate genes selected from genetic association studies of primary-open angle glaucoma, central corneal thickness, intraocular pressure, vertical cup to disc ratio, and optic nerve parameters. METHODS: Deep RNA sequencing was performed on the selected human tissues. Transcriptome analyses were performed to 1) characterize the total number of expressed genes, 2) identify the most highly expressed genes, 3) estimate the number of novel transcripts, and 4) evaluate the expression of candidate genes in each tissue. Finally, a differential gene expression analysis was conducted to compare the adult and fetal ocular tissues. RESULTS: There was an average of 12,362 protein coding genes and 3725 novel transcripts expressed in each tissue. The top most expressed genes in each tissue included SPARC (fetal cornea and TM), APOD (adult TM), CLU (adult cornea), and PTGDS (adult and fetal CB). Twenty-nine candidate genes selected from genetic association studies primarily showed high expression levels in the trabecular meshwork and cornea. Comparison of adult and fetal samples identified 2012 and 1261 differentially expressed protein-coding genes within the cornea and trabecular meshwork, respectively. CONCLUSIONS: This study has provided an unbiased glimpse into the transcriptome of three essential anterior ocular tissues, resulting in the development of several novel hypotheses. These data can be used in the future to better guide ocular research questions.
PURPOSE: To characterize the transcriptional landscape of human adult and fetal trabecular meshwork (TM), cornea, and ciliary body (CB) tissues, and to evaluate the expression level of candidate genes selected from genetic association studies of primary-open angle glaucoma, central corneal thickness, intraocular pressure, vertical cup to disc ratio, and optic nerve parameters. METHODS: Deep RNA sequencing was performed on the selected human tissues. Transcriptome analyses were performed to 1) characterize the total number of expressed genes, 2) identify the most highly expressed genes, 3) estimate the number of novel transcripts, and 4) evaluate the expression of candidate genes in each tissue. Finally, a differential gene expression analysis was conducted to compare the adult and fetal ocular tissues. RESULTS: There was an average of 12,362 protein coding genes and 3725 novel transcripts expressed in each tissue. The top most expressed genes in each tissue included SPARC (fetal cornea and TM), APOD (adult TM), CLU (adult cornea), and PTGDS (adult and fetal CB). Twenty-nine candidate genes selected from genetic association studies primarily showed high expression levels in the trabecular meshwork and cornea. Comparison of adult and fetal samples identified 2012 and 1261 differentially expressed protein-coding genes within the cornea and trabecular meshwork, respectively. CONCLUSIONS: This study has provided an unbiased glimpse into the transcriptome of three essential anterior ocular tissues, resulting in the development of several novel hypotheses. These data can be used in the future to better guide ocular research questions.
Authors: Anthony P Khawaja; Jessica N Cooke Bailey; Nicholas J Wareham; Robert A Scott; Mark Simcoe; Robert P Igo; Yeunjoo E Song; Robert Wojciechowski; Ching-Yu Cheng; Peng T Khaw; Louis R Pasquale; Jonathan L Haines; Paul J Foster; Janey L Wiggs; Chris J Hammond; Pirro G Hysi Journal: Nat Genet Date: 2018-05-21 Impact factor: 38.330
Authors: Yosuke Tanigawa; Michael Wainberg; Juha Karjalainen; Tuomo Kiiskinen; Guhan Venkataraman; Susanna Lemmelä; Joni A Turunen; Robert R Graham; Aki S Havulinna; Markus Perola; Aarno Palotie; Mark J Daly; Manuel A Rivas Journal: PLoS Genet Date: 2020-05-05 Impact factor: 5.917
Authors: Pirro G Hysi; Hélène Choquet; Anthony P Khawaja; Robert Wojciechowski; Milly S Tedja; Jie Yin; Mark J Simcoe; Karina Patasova; Omar A Mahroo; Khanh K Thai; Phillippa M Cumberland; Ronald B Melles; Virginie J M Verhoeven; Veronique Vitart; Ayellet Segre; Richard A Stone; Nick Wareham; Alex W Hewitt; David A Mackey; Caroline C W Klaver; Stuart MacGregor; Peng T Khaw; Paul J Foster; Jeremy A Guggenheim; Jugnoo S Rahi; Eric Jorgenson; Christopher J Hammond Journal: Nat Genet Date: 2020-03-30 Impact factor: 38.330