4.6 Article

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

Journal

CELLS
Volume 10, Issue 6, Pages -

Publisher

MDPI
DOI: 10.3390/cells10061561

Keywords

light damage; neurodegeneration; functional analysis; early detection; remodeling

Categories

Funding

  1. ESSSE caffe Srl
  2. Hortus Novus Srl
  3. ENEA

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Retinal neurodegeneration can affect visual perception by impairing photoreceptors and the inner retina. Early pathological signs may be hidden by compensatory mechanisms, making early diagnosis and treatment essential. Long-term analysis shows a transient functional recovery despite progressive photoreceptor loss, with different disease progression patterns in the dorsal and ventral retinas.
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.

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