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

Sci Rep. 2024 May 2;14(1):10096. doi: 10.1038/s41598-024-60444-5.

Abstract

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.

Keywords: CART; Cdh6; DBA/2J; Dyslexia; Glaucoma; Hoxd10; Mouse; Myopia; ON–OFF directionally selective; Optic nerve crush; POU6F2; Retinal ganglion cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dyslexia* / genetics
  • Dyslexia* / metabolism
  • Dyslexia* / pathology
  • Glaucoma* / genetics
  • Glaucoma* / metabolism
  • Glaucoma* / pathology
  • Humans
  • Intraocular Pressure
  • Mice
  • Mice, Inbred DBA
  • Mice, Knockout
  • Myopia* / genetics
  • Myopia* / metabolism
  • Myopia* / pathology
  • Retinal Ganglion Cells* / metabolism
  • Retinal Ganglion Cells* / pathology
  • Risk Factors

Substances

  • Pou6f2 protein, mouse