Abstract
The term retinitis pigmentosa (RP) describes a large group of hereditary retinopathies. From a cellular view, retinal degeneration is prompted by an initial death of rods, followed later by cone degeneration. This cellular progressive degeneration is translated clinically in tunnel vision, which evolves to complete blindness. The mechanism underlying the photoreceptor degeneration is unknown, but several mechanisms have been pointed out as main co-stars, inflammation being one of the most relevant. Retinal inflammation is characterized by proliferation, migration, and morphological changes in glial cells, in both microglia and Müller cells, as well as the increase in the expression of inflammatory mediators. Retinal inflammation has been reported in several animal models and clinical cases of RP, but the specific role that inflammation plays in the pathology evolution remains uncertain. Sulforaphane (SFN) is an antioxidant natural compound that has shown anti-inflammatory properties, including the modulation of glial cells activation. The present work explores the effects of SFN on retinal degeneration and inflammation, analyzing the modulation of glial cells in the RP rd10 mice model. A daily dose of 20 mg/kg of sulforaphane was administered intraperitoneally to control (C57BL/6J wild type) and rd10 (Pde6brd10) mice, from postnatal day 14 to day 20. On postnatal day 21, euthanasia was performed. Histological retina samples were used to assess cellular degeneration, Müller cells, and microglia activation. SFN administration delayed the loss of photoreceptors. It also ameliorated the characteristic reactive gliosis, assessed by retinal GFAP expression. Moreover, sulforaphane treatment regulated the microglia activation state, inducing changes in the microglia morphology, migration, and expression through the retina. In addition, SFN modulated the expression of the interleukins 1β, 4, Ym1, and arginase inflammatory mediators. Surprisingly, M2 polarization marker expression was increased at P21 and was reduced by SFN treatment. To summarize, SFN administration reduced retinal neurodegeneration and modified the inflammatory profile of RP, which may contribute to the SFN neuroprotective effect.
Highlights
Retinitis pigmentosa (RP) englobes a range of genetic retinal diseases, which cause progressive degeneration of the photoreceptor retinal layer
hematoxylin and eosin (H&E) results indicate that all the RD10 groups, treated with or without SFN, show a significant reduction in the number of row cells in the outer nuclear layer (ONL) regarding the Control groups
The RD10 SFN group suffered a significant minor cellular degeneration, pronounced in the mid and nerve periphery regions, where statistically significant differences were found between the RD10 Saline and RD10 SFN groups (p < 0.000), suggesting a delay in the neurodegeneration
Summary
Retinitis pigmentosa (RP) englobes a range of genetic retinal diseases, which cause progressive degeneration of the photoreceptor retinal layer. It has been described that the RP induces first a cellular degeneration of rods, followed by cone degeneration (Hartong et al, 2006). This histopathology pattern produces night blindness, followed by tunnel vision, and a total vision loss (Hamel, 2006; Hartong et al, 2006). There is no effective cure despite this disease affecting almost 2 million people all over the world (Farrar et al, 2002; Hartong et al, 2006). Retinal neurodegeneration induces an inflammation reaction, which has been proposed as a crucial mediator of the RP degeneration process. Chronic inflammation plays a deleterious effect on the retinal function, as has been shown in several studies (Zabel et al, 2016). It may help to find new therapeutic targets to reduce the evolution and deleterious effects of RP (Fahim, 2018)
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