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.
Highlights
These pathologies include a heterogeneous group of photoreceptor degenerations whereby populations of rods and cones are distinctly affected, i.e., rods are primarily involved in retinitis pigmentosa (RP) [3], cones in age-related macular degenerations (AMD) [3], and both rods and cones simultaneously in Leber congenital amaurosis (LCA) [4] and Stargardt’s disease (STGD1, autosomal recessive [5])
Data reported in the present study were obtained from experiments conducted on healthy control (HC) animals and animals treated with intense white light, commonly referred to as “light damaged” (LD), which were divided into twelve groups, as depicted in 24 h and sacrificed at different recovery periods (after 0, 15, 30, 45, 60, 90, and 210 days (d))
Even the short-term exposure induced a significant reduction of a-wave and b-wave amplitudes compared to the healthy control (Figure 1a,c)
Summary
Many ocular pathologies induced by several factors, such as gene mutations, environmental stresses, metabolic dysfunction, and aging, lead to reduced visual performance and eventually complete blindness caused by inflammation, mitochondrial dysfunction, synaptic remodeling, and neuronal death [2]. These pathologies include a heterogeneous group of photoreceptor degenerations whereby populations of rods and cones are distinctly affected, i.e., rods are primarily involved in retinitis pigmentosa (RP) [3], cones in age-related macular degenerations (AMD) [3], and both rods and cones simultaneously in Leber congenital amaurosis (LCA) [4] and Stargardt’s disease (STGD1, autosomal recessive [5]). These modifications could lead to considerable changes in the receptive field properties of retinal ganglion cells, the retina’s output cells, impinging on the transmission of visual information to the brain [26,27,28]
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