Abstract
Purpose: :
Work in our laboratory and others has revealed striking neuritogenesis in the neural retina subsequent to photoreceptor stress and degeneration. While the initiators of this process remain unknown, our data indicate that major changes in retinoid processing occur prior to neuritogenesis. We hypothesize that alterations in retinoic acid (RA) signaling may influence the evolution of neuritogenesis and subsequent retinal remodeling.
Methods: :
Adult balb/c albino mice were exposed to constant intense light (24 h) by excluding one normal night cycle (12 h) to establish the light-induced retinal degeneration (LIRD) animal model. Retinas were harvested at post-light exposure day (pLX) 0, 1, 7, 30, 60, 90 and 120 for RA signaling analysis with morphological, metabolic profiling and biochemical parameters.
Results: :
Cellular retinoic acid-binding proteins II (CRABP II), RA receptors α, β (RARα, β), and retinoid receptors β, γ (RXRβ, γ) were expressed in inner nuclear layer (INL) and ganglion cell layer (GCL). RARγ and RXRα were not detected in control retina, but RARγ expression was immediately initiated by light stress and peaked at pLX7. The levels of CRABP II, RARβ, RXRβ, RXRγ, and müller cells marker cellular retinaldehyde-binding protein (CRALBP) were up-regulated then fluctuated in the neural retina after light stress, while RARα level had no alteration. These changes were followed by bipolar cell neuritogenesis revealed by PKCα staining in the survivor zone where the gross histology of the neural retina seemed normal. However, as expected, signals of the examined RA signaling components were reduced in INL of the LIRD zone, where photoreceptor loss and early dendritic remodeling occurred.
Conclusions: :
Even though the gross histology of the neural retina in the survivor zone seems normal early in LIRD, RA signaling displays large alterations, suggesting potential RA signaling pathways responsible for neuritogenesis and reactive neuronal plasticity. Deficiency of RA signaling may contribute to neurite degeneration.
Keywords: retinoids/retinoid binding proteins • retinal degenerations: cell biology • stress response