The susceptibility of the retina to photochemical damage from visible light

Abstract

The photoreceptor/RPE complex must maintain a delicate balance between maximizing the absorption of photons for vision and retinal image quality while simultaneously minimizing the risk of photodamage when exposed to bright light. We review the recent discovery of two new effects of light exposure on the photoreceptor/RPE complex in the context of current thinking about the causes of retinal phototoxicity. These effects are autofluorescence photobleaching in which exposure to bright light reduces lipofuscin autofluorescence and, at higher light levels, RPE disruption in which the pattern of autofluorescence is permanently altered following light exposure. Both effects occur following exposure to visible light at irradiances that were previously thought to be safe. Photopigment, retinoids involved in the visual cycle, and bisretinoids in lipofuscin have been implicated as possible photosensitizers for photochemical damage. The mechanism of RPE disruption may follow either of these paths. On the other hand, autofluorescence photobleaching is likely an indicator of photooxidation of lipofuscin. The permanent changes inherent in RPE disruption might require modification of the light safety standards. AF photobleaching recovers after several hours although the mechanisms by which this occurs are not yet clear. Understanding the mechanisms of phototoxicity is all the more important given the potential for increased susceptibility in the presence of ocular diseases that affect either the visual cycle and/or lipofuscin accumulation. In addition, knowledge of photochemical mechanisms can improve our understanding of some disease processes that may be influenced by light exposure, such as some forms of Leber’s congenital amaurosis, and aid in the development of new therapies. Such treatment prior to intentional light exposures, as in ophthalmic examinations or surgeries, could provide an effective preventative strategy.

Two-photon microscopy reveals early rod photoreceptor cell damage in light-exposed mutant mice

“…atRAL along with its derivative products likely are the initiators of photoreceptor cell pathology for several reasons: (i) phototransduction is the only light-sensitive pathway in ROS and this process involves the conversion of retinoids and generation of atRAL (62,63); (ii) such light-induced degeneration can be prevented by pretreatment with retinoid cycle inhibitors (Fig. S3); and (iii) both retinoids and their condensation products are known to produce cellular toxicity and death (12,18,31,64,65). Retinal pathology could also result from mitochondrial dysfunction, because lipophilic unsaturated compounds such as retinoids can also act as electron acceptors that compromise ATP production (66)(67)(68)(69).…”

Light damage to the retina: an historical approach

“…Table 1 summarizes the main properties of the two types of retinal damage. 6,7 For the sake of completeness a third type of light damage to the retina is mentioned here, photodisruption. This requires a pulsed laser often operating in the infrared.…”

“…Patients suffering from diseases affecting the visual cycle, such as Stargardt's dystrophy, Best disease, or Oguchi disease, should require extra care as they might suffer increased susceptibility to light damage, as was found in animal models. 7,32 Continued research on photochemical damage is relevant because many open questions remain, only some of them treated in this limited review. An action spectrum for freely moving animals exposed to continuous light for one or more natural days, thus in the 'Noell conditions', is still lacking, and the search for the photosensitizers underlying the Ham-type action spectrum is far from complete.…”

“…Peculiarly, an action spectrum for mice, about the most frequently used animal model, is not available. 15 New questions are risen after discovery of unexpected changes in images of the pigment epithelium after long exposures to yellow light, 7 and recently even after exposures to infrared radiation, argued to be photochemical in nature. 33 Moreover, photochemical damage can be used as a model for aging mechanisms.…”

“…Prevention or repair of photochemical light damage might therefore lead to prevention or cure of damage by aging. 7 …”