Prolonged Inner Retinal Photoreception Depends on the Visual Retinoid Cycle

Area of Science:

• Ophthalmology
• Neuroscience
• Cell Biology

Background:

• Mammals possess intrinsically photosensitive retinal ganglion cells (ipRGCs) utilizing melanopsin for non-image-forming visual responses.
• Photopigment regeneration, crucial for light sensitivity, typically relies on the retinoid cycle in the retinal pigment epithelium (RPE) for rods and cones.
• ipRGCs' distance from the RPE led to the hypothesis of RPE-independent melanopsin regeneration.

Purpose of the Study:

• To investigate the role of the RPE in melanopsin regeneration and function.
• To determine if the RPE is required for sustained ipRGC photoresponses during prolonged light exposure.

Main Methods:

• In vitro electrophysiological recordings of rat ipRGCs.
• In vivo pupillometry in mice and rats.
• Inhibition of the retinoid cycle and Müller glia.

Main Results:

• RPE removal or retinoid cycle inhibition significantly reduced the sustained photoresponses of ipRGCs and pupil reflexes.
• Melanopsin-based responses were sustained with a functional RPE but became transient without it.
• An 11-cis-retinal analog partially restored sustained responses in RPE-separated retinas.

Conclusions:

• The RPE plays a critical role in the continuous regeneration of melanopsin during prolonged, intense light exposure.
• 11-cis-retinal, supplied by the RPE possibly via Müller cells, is essential for this sustained regeneration.
• Findings have implications for RPE-related eye diseases and retinoid-based therapies like isotretinoin.