Abstract

Phototoxicity animal models have been largely studied due to their degenerative communalities with human pathologies, e.g., age-related macular degeneration (AMD). Studies have documented not only the effects of white light exposure, but also other wavelengths using LEDs, such as blue or green light. Recently, a blue LED-induced phototoxicity (LIP) model has been developed that causes focal damage in the outer layers of the superior-temporal region of the retina in rodents. In vivo studies described a progressive reduction in retinal thickness that affected the most extensively the photoreceptor layer. Functionally, a transient reduction in a- and b-wave amplitude of the ERG response was observed. Ex vivo studies showed a progressive reduction of cones and an involvement of retinal pigment epithelium cells in the area of the lesion and, in parallel, an activation of microglial cells that perfectly circumscribe the damage in the outer retinal layer. The use of neuroprotective strategies such as intravitreal administration of trophic factors, e.g., basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF) or pigment epithelium-derived factor (PEDF) and topical administration of the selective alpha-2 agonist (Brimonidine) have demonstrated to increase the survival of the cone population after LIP.

Highlights

  • The deleterious effect of light is classified depending on the type of damage induced [16,60]: (i) photomechanical damage: produced by rapid inputs of light which cause compressive or tensile forces and lead to microbubbles formation and the destruction of retinal pigment epithelium (RPE) and other cells; (ii) photothermal damage: photons of light can be absorbed by retinal tissue, specially by the melanosomes of the RPE and melanocytes of the choroid, and produce the denaturation of molecules and formation of abnormal molecular linkage which lead to the loss of function of the cells; (iii) photochemical damage: light energy excites the electron of different molecules of the retina

  • Cone degeneration analysis was performed on the area of damage within a 0.9 mm diameter prefixed circular area (PCA) and showed a significant reduction of arrestin+ cones at 3 days after LED-induced phototoxicity (LIP) that progressed to 7 days later, when cones within the PCA decreased by 35%

  • The results showed that there was no significant difference between administering the drug on the same day of LIP induction or the day before and its administration had a positive effect on cone rescue within the PCA, with 49–52% rescue of S-cones and 14–17% rescue of L-cones in albino rats [37] and 36–46% rescue of S-cones in albino mice [39]

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Summary

Age Related Macular Degeneration

Age-related macular degeneration (AMD) is a chronic, progressive degeneration of the retina that causes loss of central vision in people over 50 years of age [1,2]. Numerous risk factors have been identified [2]. Animal research has shown that chronic exposure to blue or ultraviolet light is harmful to photoreceptors and the RPE [15,16]. Clinical studies have documented the deleterious effects of acute exposure to light on the retina [17], the effects of chronic exposure to light remain to be shown. Different animal models of phototoxicity have been developed to study light-induced retinal degeneration in order to better understand AMD and prevent its onset [11,18,19]

Phototoxicity Models
LED Phototoxicity Models
Diffuse LED Phototoxicity Models
Focal LED Phototoxicity Models
Distribution of Cone Population in Rats and Mice
Toxic Effects of Focal LIP on the Retina
In Vivo SD-OCT Observations in the Focal LIP
Ex Vivo Histological Observations in Focal LIP
Microglial Reaction in Focal Phototoxicity Models
RPE Degeneration in a Focal Phototoxicity Model
Neuroprotection
Neuroprotection in Focal Phototoxicity Models
Neurotrophic Factors
Minocycline
Limitations of the Model
Findings
Concluding Remarks
Full Text
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