Neuroinflammation as a Therapeutic Target in Retinitis Pigmentosa and Quercetin as Its Potential Modulator

Abstract

The retina is a multilayer neuronal tissue located in the back of the eye that transduces the environmental light into a neural impulse. Many eye diseases caused by endogenous or exogenous harm lead to retina degeneration with neuroinflammation being a major hallmark of these pathologies. One of the most prevalent retinopathies is retinitis pigmentosa (RP), a clinically and genetically heterogeneous hereditary disorder that causes a decline in vision and eventually blindness. Most RP cases are related to mutations in the rod visual receptor, rhodopsin. The mutant protein triggers inflammatory reactions resulting in the activation of microglia to clear degenerating photoreceptor cells. However, sustained insult caused by the abnormal genetic background exacerbates the inflammatory response and increases oxidative stress in the retina, leading to a decline in rod photoreceptors followed by cone photoreceptors. Thus, inhibition of inflammation in RP has received attention and has been explored as a potential therapeutic strategy. However, pharmacological modulation of the retinal inflammatory response in combination with rhodopsin small molecule chaperones would likely be a more advantageous therapeutic approach to combat RP. Flavonoids, which exhibit antioxidant and anti-inflammatory properties, and modulate the stability and folding of rod opsin, could be a valid option in developing treatment strategies against RP.

Cuscuta chinensis Lam. Protects Against Light-Induced Retinal Degeneration: Therapeutic Implications for Photoreceptor Degenerative Disorders

“…It is also worth noting that quercetin, a type of flavonoids found in CCL, has been shown to mitigate light-induced retinal degeneration in rats ( Koyama et al, 2019 ). The pharmacological potential of quercetin in attenuating neuroinflammation accompanying photoreceptor degeneration has also been demonstrated in a mouse model of RP ( Ortega and Jastrzebska, 2021 ). In addition, it has been reported that kaempferol, another flavonoid component of CCL, protects against oxidizing agent sodium iodate-induced photoreceptor degeneration ( Du et al, 2018 ).…”

Outer Retinal Tubulation in Bietti Crystalline Dystrophy Associated With the Retinal Pigment Epithelium Atrophy

“…The release of inflammatory factors by injured photoreceptors and RPE may cause retinal inflammatory microenvironment and further damage the integrity of the outer retina. 32 , 33 As the presence of ORT is formed by scrolled ELM, we hypothesized that ORT may border atrophic lesions therefore isolating the local inflammatory microenvironment and thus slowing down the visual loss in late-stage BCD.…”

Late gene therapy limits the restoration of retinal function in a mouse model of retinitis pigmentosa

“…As a final measure of retinal structure following time-dependent rescue of Cngb1, we investigated the activation of Müller glia by immunolabeling glial fibrillary acid protein (GFAP) 16 . This marker indicates a retinal inflammatory response, which is present in patients with RP [17][18][19] . While this response can protect the retina from damage (e.g., by releasing neuroprotective molecules) 20,21 , prolonged activation can increase tissue damage through the release of pro-inflammatory markers 22 .…”