Abstract
Purpose :
Central corneal thickness (CCT) is one of the most heritable ocular traits and it is also a phenotypic risk factor for primary open angle glaucoma. Previously we identified POU6F2 as a gene modulating CCT in the mouse using the BXD RI strain set as a genetic reference panel. In collaboration with Janey Wiggs we found that POU6F2 is a potential candidate for glaucoma risk in the NEIGHBORHOOD open-angle glaucoma genome wide association study. The first hint that POU6F2 could link CCT to glaucoma risk came from studies of the developing eye where POU6F2 is found in the developing cornea and in developing retinal ganglion cells (RGCs). Furthermore, in the DBA/2J mouse model of glaucoma the POU6F2 RGCs were some of the first cells to die. The present study is designed to characterize the POU62-positive RGCs.
Methods :
We have now examined the Pou6f2-null mouse, for effects on corneal thickness and RGC number. In addition, we have used the Thy1-YFP-H mouse to identify the structure of the RGCs in the retina that are POU6F2 positive. To examine the visual capacity of the Pou6f2-null mouse we used optokinetic tracking (OKT) defining acuity and contrast sensitivity relative to wild-type littermates.
Results :
In the retina POU6F2 labels 16% of the RGCs and in 3D constructions of POU6F2-positive, Thy1-YFP-H labeled cells had dendrites in the inner plexiform layer that were bistratified. These RGCs have the appearance of on-off directionally selective cells. When we examined the retina of the Pou6f2-null mouse there was a loss of 16% of the cells relative to the wild type littermate. Based on preliminary data these cells appear to be the POU6F2 positive cells. To determine if the loss of these cells could affect visual function, we examined the performance of the mice using OKT. We found that the contrast sensitivity function of the Pou6f2-null mouse was severely depressed relative to the wild type littermates. There was also a significant (p < 0.05 student t test) decrease in visual acuity.
Conclusions :
These data identify POU6F2 as a factor contributing to the correlation between CCT and risk fordeveloping glaucoma with POU6F2 being expressed in on-off directionally selective cells.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.