Abstract
Retinal degeneration (RD) encompasses a family of diseases that lead to photoreceptor death and visual impairment. Visual decline due to photoreceptor cell loss is further compromised by emerging spontaneous hyperactivity in inner retinal cells. This aberrant activity acts as a barrier to signals from the remaining photoreceptors, hindering therapeutic strategies to restore light sensitivity in RD. Gap junctions, particularly those expressed in AII amacrine cells, have been shown to be integral to the generation of aberrant activity. It is unclear whether gap junction expression and coupling are altered in RD. To test this, we evaluated the expression and phosphorylation state of connexin36 (Cx36), the gap junction subunit predominantly expressed in AII amacrine cells, in two mouse models of RD, rd10 (slow degeneration) and rd1 (fast degeneration). Using Ser293-P antibody, which recognizes a phosphorylated form of connexin36, we found that phosphorylation of connexin36 in both slow and fast RD models was significantly greater than in wildtype controls. This elevated phosphorylation may underlie the increased gap junction coupling of AII amacrine cells exhibited by RD retina.
Highlights
Retinal degeneration (RD) encompasses a family of diseases originating from genetic alteration in more than 100 genes, as well as acquired conditions, such as trauma caused by excessive light exposure, and aging (Menzler et al, 2014)
We will focus on serine 293 (Ser293)-P expression in the mouse inner plexiform layer (IPL), which contains the processes of AII amacrine cells
The major finding of this study was that connexin36 gap junctions in AII amacrine cells exhibit elevated phosphorylation in both fast and slow mouse models of RD, while the general expression level of connexin36 remained unchanged. This elevated phosphorylation may underlie the increased gap junction coupling of AII amacrine cells exhibited by RD retina (Ivanova et al, 2015)
Summary
Retinal degeneration (RD) encompasses a family of diseases originating from genetic alteration in more than 100 genes, as well as acquired conditions, such as trauma caused by excessive light exposure, and aging (Menzler et al, 2014). While the most apparent physiological consequence of RD is the progressive loss of photoreceptors, surviving inner retinal neurons form a dysfunctional network that generates aberrant synaptic activity (Pu et al, 2006; Marc et al, 2007; Stasheff, 2008). Similar rhythmic activity has been observed in higher visual centers in RD models (Drager and Hubel, 1978; Sauve et al, 2001; Ivanova et al, 2015) and may be the cause of flashing sensations reported by RD patients (Lepore, 1990; Murtha and Stasheff, 2003). A finding showing that reducing this aberrant activity can restore visual responses in degenerated retina provides new insights into our understanding of degenerative process and opens up a new venue for therapy (Toychiev et al, 2013a)
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