Blue light induced retinal damage

Abstract: Visual perception results from a response to radiation between 400 and 760 mu reaching the retina. Photoreceptor cells are differentiated post-mitotic retinal neurons uniquely adapted for the efficient capture of photons and for the initiation of visual transduction. Photoreceptors are normally subjected to incident light while being maintained in an oxygen rich environment to satisfy the highest metabolic demand of any cells in the body. Thus the potential for visual cell injury as a result of photochemical damage is great. Since the retinal sensitivity to the damaging light increases towards the blue end of the visible spectrum, blue light is considered to be most hazardous to the retina. The project started with the establishment of a novel device enabling light exposure to be carried out under such "natural" conditions that no anesthesia was applied and the exposure regime was designed as relatively lower irradiance versus longer exposure durations. The innovation of the rotating cage ensures meaningful dose-response estimation. A light source with the emission of 400-480 nm, peaking at 420 nm, was selected. Albino Sprague-Dawley rats were employed due to their high sensitivity to light damage. Six days after continuous light exposure for 6 hours, blue light damaged both photoreceptor cells and epithelial cells. Irrespective of a uniform delivery of the light to the retina, the blue light resulted in an uneven distribution of damage that is intrinsically expressed at the upper temporal quadrant, with more severe damage in the central part than periphery. The photoreceptor damage by blue light was characterized by progressive condensation and margination of the chromatin, shrinkage or convolution and fragmentation of the nucleus, condensation of the cytoplasm, and formation of apoptotic bodies along with rapid removal of dying cells from damaged areas in the absence of inflammatory response. A wave of massive TUNEL labeling of photoreceptor nuclei peaking at 8-16 hours during 24 hours after exposure to blue light was accompanied by the multiples of internucleosomal cleavage of 180-200 base pairs. Therefore, photoreceptor cell apoptosis is seen early after the retina is damaged by blue light. The apoptosis response is geographically correlated with the loss of the photoreceptor cells in the outer nuclear layer. In subsequent studies procaspase-3 and procaspase-9 proteins were shown to be constitutively expressed in the rat retina and were upregulated after in vivo exposure to blue light. Meanwhile, increased cleavage of caspase-3 or caspase-9 into the active fragments and elevation of caspase-3 or caspase-9 like activity were detected, peaking at 16 hours and 8 hours, respectively postexposure. These activated caspases were located in the outer nuclear layer and predominantly in the superior central part of the temporal quadrant. Moreover, cytochrome c was shown to be released from the mitochondria with maximum at 16 hours, thereby corresponding to the peak response of apoptosis after exposure to blue light. Finally, that the supplementary ascorbic acid protects retinal damage induced by green light rather than blue light implies that the damaging mechanism is unique in blue light-mediated retinal damage. In conclusion, the current study delineates the vulnerability of the photoreceptor to blue light, providing a mechanistic explanation for blue light hazard in the retina. It supports the suggestion that lifetime exposure of the retina to light affects its rate of ageing, in turn contributing to the pathogeneses of age-related macular degeneration.