Curcumin Delays Retinal Degeneration by Regulating Microglia Activation in the Retina of rd1 Mice

Abstract

Background/Aims: Retinitis pigmentosa (RP) is characterized by degeneration of photoreceptors, and there are currently no effective treatments for this disease. However, curcumin has shown neuroprotectant efficacy in a RP rat and swine model, and thus, may have neuroprotective effects in this disease. Methods: Immunofluorescence staining, electroretinogram recordings, and behavioral tests were used to analyze the effects of curcumin and the underlying mechanism in retinal degeneration 1 (rd1) mice. Results: The number of apoptotic cells in the retina of rd1 mice at postnatal day 14 significantly decreased with curcumin treatment and visual function was improved. The activation of microglia and secretion of chemokines and matrix metalloproteinases in the retina were inhibited by curcumin. These effects were also observed in a co-culture of BV2 microglial cells and retina-derived 661W cells. Conclusions: Curcumin delayed retinal degeneration by suppressing microglia activation in the retina of rd1 mice. Thus, it may be an effective treatment for neurodegenerative disorders such as RP.

Epothilone B Benefits Nigral Dopaminergic Neurons by Attenuating Microglia Activation in the 6-Hydroxydopamine Lesion Mouse Model of Parkinson’s Disease

“…Both cell types were maintained in DMEM supplemented with 10% fetal bovine serum, 1% GlutaMax, and 1% penicillin-streptomycin (Gibco, Life Technologies, Grand Island, NY, USA). MN9D cells were seeded onto 6-well plates at a density of 3 × 10 5 cells/well 12 h for attachment (Li Z. et al, 2016 ; Wang et al, 2017 ). BV2 cells were seeded into the transwell inserts (Millipore), which corresponds to a 6-well plate at a seeding density of 2 × 10 5 cells per well.…”

Mechanisms of Photoreceptor Death in Retinitis Pigmentosa

“…Pharmacological inhibition of microglial activation and cytokine release has been shown to reduce photoreceptor cell death [ 107 , 108 ]. Down-regulation of pathways involved in innate immunity and inflammation were also found to reduce retinal degeneration and preserve photoreceptor function in Rho P347S mice [ 109 ].…”

“…Curcumin, a compound derived from turmeric, has been shown to have antioxidant and anti-apoptotic properties [ 194 , 195 ]. Curcumin was also found to inhibit the activation of microglia and release of chemokines in rd1 mice, resulting in improved photoreceptor survival [ 107 ]. Treatment of COS-7 cells expressing P23H rhodopsin with curcumin resulted in the dissociation of protein aggregates and reduced levels of the ER stress markers BiP and CHOP [ 196 ].…”

Rescue of Retinal Degeneration in rd1 Mice by Intravitreally Injected Metformin

“…In contrast with the P23H RP mouse model, rd1 mice carry mutations in the β subunit of rod cGMP-phosphodiesterase (PDE6β); these mutations result in the accumulation of cGMP in the retina (Bowes et al, 1990; Wang et al, 2017). This accumulation affects the cyclic nucleotide-gated (CNG) channels in the outer segment membrane and causes deleterious calcium (Ca 2+ ) influx, and the calcium overloading causes rapid rod cell death (Paquet-Durand et al, 2011).…”

“…Whether metformin produces a neuroprotective effect in other RD mouse models in addition to P23H RP mice is unclear. Rd1 mouse is an animal model of rapid retinal photoreceptor degeneration; the phenotype is mainly caused by mutations in the β subunit of rod cGMP-phosphodiesterase (PDE6β), which results in cGMP accumulation in the retina (Wang et al, 2017), eventually causing early onset severe retinal degeneration (Bowes et al, 1990). Rd1 mice have served as a model for human RP for more than 30 years, and mutations in rd1 mice are homologous to those underlying human pathogenic causes (Li et al, 2016; Xu et al, 2018).…”