Selective Assembly of TRPC Channels in the Rat Retina during Photoreceptor Degeneration

TL;DR

This study explores how TRPC1 and TRPC5 calcium channels in rat retinas change during retinal degeneration, potentially helping protect inner retinal cells.

Contribution

The study reveals that TRPC1/5 heteromers increase during retinal degeneration, possibly delaying inner retinal cell death.

Findings

TRPC1 and TRPC5 physically interact in the innermost retina and this interaction increases with photoreceptor loss.

TRPC1/5 heteromers function in both healthy and degenerating retinas, with TRPC1 playing a protective role.

TRPC5 also interacts with STIM1 in Müller and retinal ganglion cells during degeneration.

Abstract

Transient receptor potential canonical (TRPC) channels are calcium channels with diverse expression profiles and physiological implications in the retina. Neurons and glial cells of rat retinas with photoreceptor degeneration caused by retinitis pigmentosa (RP) exhibit basal calcium levels that are above those detected in healthy retinas. Inner retinal cells are the last to degenerate and are responsible for maintaining the activity of the visual cortex, even after complete loss of photoreceptors. We considered the possibility that TRPC1 and TRPC5 channels might be associated with both the high calcium levels and the delay in inner retinal degeneration. TRPC1 is known to mediate protective effects in neurodegenerative processes while TRPC5 promotes cell death. In order to comprehend the implications of these channels in RP, the co-localization and subsequent physical interaction between TRPC1 and TRPC5 in healthy retina (Sprague-Dawley rats) and degenerating (P23H-1, a model of RP) retina were detected by immunofluorescence and proximity ligation assays. There was an overlapping signal in the innermost retina of all animals where TRPC1 and TRPC5 physically interacted. This interaction increased significantly as photoreceptor loss progressed. Both channels function as TRPC1/5 heteromers in the healthy and damaged retina, with a marked function of TRPC1 in response to retinal degenerative mechanisms. Furthermore, our findings support that TRPC5 channels also function in partnership with STIM1 in Müller and retinal ganglion cells. These results suggest that an increase in TRPC1/5 heteromers may contribute to the slowing of the degeneration of the inner retina during the outer retinal degeneration.

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