Journal Article

POU6F2, a risk factor for glaucoma, myopia and dyslexia, labels specific populations of retinal ganglion cells

Lin, Fangyu, Boatright, Jeffrey H., Li, Ying, Jardines, Sandra, King, Rebecca, Geisert, Eldon E., Wang, Jiaxing, Chrenek, Micah A., Wiggs, Janey L.

2024

Overview

Pou6f2 is a genetic connection between central corneal thickness (CCT) in the mouse and a risk factor for developing primary open-angle glaucoma. POU6F2 is also a risk factor for several conditions in humans, including glaucoma, myopia, and dyslexia. Recent findings demonstrate that POU6F2-positive retinal ganglion cells (RGCs) comprise a number of RGC subtypes in the mouse, some of which also co-stain for Cdh6 and Hoxd10. These POU6F2-positive RGCs appear to be novel of ON–OFF directionally selective ganglion cells (ooDSGCs) that do not co-stain with CART or SATB2 (typical ooDSGCs markers). These POU6F2-positive cells are sensitive to damage caused by elevated intraocular pressure. In the DBA/2J mouse glaucoma model, heavily-labeled POU6F2 RGCs decrease by 73% at 8 months of age compared to only 22% loss of total RGCs (labeled with RBPMS). Additionally, Pou6f2 −/− mice suffer a significant loss of acuity and spatial contrast sensitivity along with an 11.4% loss of total RGCs. In the rhesus macaque retina, POU6F2 labels the large parasol ganglion cells that form the magnocellular (M) pathway. The association of POU6F2 with the M-pathway may reveal in part its role in human glaucoma, myopia, and dyslexia.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/378/2613 / 631/378/2613/1786 / 692/699/3161 / Acuity / Animals / Cdh6 / Cornea / Disease Models, Animal / Dyslexia / Dyslexia - genetics / Dyslexia - metabolism / Dyslexia - pathology / Glaucoma / Glaucoma - genetics / Glaucoma - metabolism / Glaucoma - pathology / Hoxd10 / Humanities and Social Sciences / Humans / Intraocular Pressure / Mice / Mice, Inbred DBA / Mice, Knockout / multidisciplinary / Myopia / Myopia - genetics / Myopia - metabolism / Myopia - pathology / POU6F2 / Retina / Retinal ganglion cell / Retinal ganglion cells / Retinal Ganglion Cells - metabolism / Retinal Ganglion Cells - pathology / Risk Factors / Science / Science (multidisciplinary)