PTEN Expression Regulates Gap Junction Connectivity in the Retina

Ashley M Chen; Shaghauyegh S Azar; Alexander Harris; Nicholas C Brecha; Luis Pérez de Sevilla Müller

doi:10.3389/fnana.2021.629244

PTEN Expression Regulates Gap Junction Connectivity in the Retina

Front Neuroanat. 2021 May 20:15:629244. doi: 10.3389/fnana.2021.629244. eCollection 2021.

Authors

Ashley M Chen¹, Shaghauyegh S Azar¹, Alexander Harris¹, Nicholas C Brecha^{1

2

3

4}, Luis Pérez de Sevilla Müller¹

Affiliations

¹ Department of Neurobiology, David Geffen School of Medicine at Los Angeles, University of California, Los Angeles, Los Angeles, CA, United States.
² Stein Eye Institute, David Geffen School of Medicine at Los Angeles, University of California, Los Angeles, Los Angeles, CA, United States.
³ CURE Digestive Diseases Research Center, David Geffen School of Medicine at Los Angeles, University of California, Los Angeles, Los Angeles, CA, United States.
⁴ Veterans Administration Greater Los Angeles Health System, Los Angeles, CA, United States.

Abstract

Manipulation of the phosphatase and tensin homolog (PTEN) pathway has been suggested as a therapeutic approach to treat or prevent vision loss due to retinal disease. In this study, we investigated the effects of deleting one copy of Pten in a well-characterized class of retinal ganglion cells called α-ganglion cells in the mouse retina. In Pten ^+/- retinas, α-ganglion cells did not exhibit major changes in their dendritic structure, although most cells developed a few, unusual loop-forming dendrites. By contrast, α-ganglion cells exhibited a significant decrease in heterologous and homologous gap junction mediated cell coupling with other retinal ganglion and amacrine cells. Additionally, the majority of OFF α-ganglion cells (12/18 cells) formed novel coupling to displaced amacrine cells. The number of connexin36 puncta, the predominant connexin that mediates gap junction communication at electrical synapses, was decreased by at least 50% on OFF α-ganglion cells. Reduced and incorrect gap junction connectivity of α-ganglion cells will affect their functional properties and alter visual image processing in the retina. The anomalous connectivity of retinal ganglion cells would potentially limit future therapeutic approaches involving manipulation of the Pten pathway for treating ganglion cell degeneration in diseases like glaucoma, traumatic brain injury, Parkinson's, and Alzheimer's diseases.

Keywords: PTEN (phosphatase and tensin homolog deleted on chromosome 10); connexin (Cx36); degeneration; gap junction (connexin); retina; retinal ganglion cells.

Abstract

Grants and funding