The Timecourses of Functional, Morphological, and Molecular Changes Triggered by Light Exposure in Sprague–Dawley Rat Retinas

Abstract

Retinal neurodegeneration can impair visual perception at different levels, involving not only photoreceptors, which are the most metabolically active cells, but also the inner retina. Compensatory mechanisms may hide the first signs of these impairments and reduce the likelihood of receiving timely treatments. Therefore, it is essential to characterize the early critical steps in the neurodegenerative progression to design adequate therapies. This paper describes and correlates early morphological and biochemical changes in the degenerating retina with in vivo functional analysis of retinal activity and investigates the progression of neurodegenerative stages for up to 7 months. For these purposes, Sprague–Dawley rats were exposed to 1000 lux light either for different durations (12 h to 24 h) and examined seven days afterward (7d) or for a fixed duration (24 h) and monitored at various time points following the exposure (up to 210d). Flash electroretinogram (fERG) recordings were correlated with morphological and histological analyses to evaluate outer and inner retinal disruptions, gliosis, trophic factor release, and microglial activation. Twelve hours or fifteen hours of exposure to constant light led to a severe retinal dysfunction with only minor morphological changes. Therefore, early pathological signs might be hidden by compensatory mechanisms that silence retinal dysfunction, accounting for the discrepancy between photoreceptor loss and retinal functional output. The long-term analysis showed a transient functional recovery, maximum at 45 days, despite a progressive loss of photoreceptors and coincident increases in glial fibrillary acidic protein (GFAP) and basic fibroblast growth factor-2 (bFGF-2) expression. Interestingly, the progression of the disease presented different patterns in the dorsal and ventral retina. The information acquired gives us the potential to develop a specific diagnostic tool to monitor the disease’s progression and treatment efficacy.

Dietary Supplementation of Antioxidant Compounds Prevents Light-Induced Retinal Damage in a Rat Model

“…The activation of the apoptotic cascade is paralleled by photoreceptor loss as determined by a drastic decrease in ONL thickness. As a consequence of photoreceptor loss, both scotopic and photopic ERG responses are reduced in amplitude thus indicating a drastic impairment of the visual function, in line with previous reports [26].…”

“…The protocol used here for light-induced damage is in line with that reported in previous studies in which the duration and the intensity of light exposure needed to cause morphological and functional damage to the retina have been determined [ 26 ]. In particular, rats were dark-adapted overnight and then their pupils were dilated by 1% tropicamide eye drops (Allergan S.p.A., Rome, Italy) immediately before the light exposure.…”

Cone Photoreceptor Loss in Light-Damaged Albino Rats

“…Other studies have demonstrated a decrease in both rod- and cone-driven function through reductions in both light- and dark-adapted electroretinography (ERG) b-wave amplitudes and thresholds [ 23 ]. Recently, Riccitelli and colleagues thoroughly examined the light damage effects of brief (12–24 h) 1000 lux exposures on retinal morphology, anatomy, and function, as well as molecular signatures [ 24 ]. They found that functional losses were detectable prior to anatomical changes and that loss of 75% of cones resulted in an immediate loss of photopic b-waves of similar magnitude.…”

Short- and Long-Term Study of the Impact of Focal Blue Light-Emitting Diode-Induced Phototoxicity in Adult Albino Rats

“…However, it has been documented that there are other environmental factors that may favour the onset of this disease, such as exposure to light [ 5 , 6 , 7 ]. Because of this, many animal studies have focused on the study of the degeneration process of photoreceptors, both in inherited models [ 8 , 9 , 10 , 11 , 12 , 13 ] and in models of induced phototoxicity [ 5 , 14 , 15 , 16 , 17 , 18 ]. In the development of phototoxicity induction models, many recent studies have used light-emitting diode (LED) sources that show a deleterious effect of the light with an involvement of the retina, more aggressive in the outer region affecting photoreceptors and retinal pigment epithelium (RPE) cells [ 15 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ].…”