Toxic photochemistry and signaling repercussions of blue light in cells exposed to retinal

Abstract

Age‐related visual damage by blue light and its adverse effects on quality of life for many people >55 yrs have been well documented. Eliminating blue wavelengths has been shown to reduce age‐related visual impairment and facilitate vision preservation in the elderly. The blue region of the visible spectrum is abundant in sunlight and common electronic light emitters. Many adults receive increased ultraviolet and blue light exposure upon retirement by moving closer to the tropics and spending more time outdoors. The cornea and lens of the eye are largely opaque to ultraviolet, while blue light readily permeates into the retina. We propose that all‐trans‐retinal (ATR), the light‐sensitive chromophore released from photoexcited photopigments in the retina, could induce age‐related vision impairment. Our data demonstrate that exposing cells incubated with ATR and exposed to blue light or sunlight permanently distorted the chemical properties of the crucial signaling lipid PIP2 and disrupted its subcellular location and signaling. Similar conditions permanently displaced G proteins in the phototransduction cascade and Ras family G proteins from the plasma membrane to the cell interior. Chemical evidence shows the oxidation of their farnesyl lipid anchor during this perturbation. Upon ATR and blue light, the percent positivity for TUNEL stain, indicating DNA damage, is significantly higher in primary cells isolated from mouse retina. We also show α‐Tocopherol, a lipid‐soluble antioxidant, inhibits the above cellular photodamage. Therefore, we now ask the critical question: could resident ATR concentrations in photoreceptor cells cause retina neurodegeneration upon physiologically relevant light exposures?