👤 V Flati

Retinal neurodegenerative diseases such as Age-related Macular Degeneration (AMD) and Retinitis Pigmentosa cause irreversible vision loss due to the limited regenerative capacity of the mammalian retina. Cerium oxide nanoparticles (nanoceria) are emerging therapeutics against oxidative stress and inflammation, major drivers of photoreceptor degeneration, and have demonstrated morphological and functional neuroprotection in preclinical models. However, the genome-wide transcriptional mechanisms underlying these effects remain incompletely characterized. We performed retinal transcriptomic analysis in a rat AMD model induced by intense light and treated intravitreally with nanoceria. Six groups were analyzed: control, light damage, vehicle, nanoceria, vehicle + light damage, and nanoceria + light damage. Light damage activated inflammatory and apoptotic programs, with upregulation of cytokines (Tnf, Il6, Il1b, Ccl2) and downregulation of photoreceptor genes (Rho, Pde6a/b, Gnat1). Nanoceria treatment counteracted these effects, suppressing pro-inflammatory mediators, restoring antioxidative genes (Nfe2l2, Gclc, Sod2), and enhancing neuroprotective factors (Bdnf, Cntf, Ngf). Pathway analyses revealed inhibition of TNF/NF-κB/IL-17 signaling and activation of PI3K-Akt, JAK-STAT, and neurotrophin pathways. Unexpectedly, nanoceria also modulated amino acid and insulin metabolism (Ass1, Cps1, Insr, Irs1, Slc2a4) and reactivated transcription factors (Ascl1, Sox2, Notch1) typically silent in adult retina. Our findings highlight nanoceria as a multifunctional therapeutic that mitigates retinal degeneration by coordinating oxidative, inflammatory, and regenerative responses. Together with prior morphological and functional validations, these results support the translational potential of nanoceria for treating retinal neurodegenerative diseases. Show less

Obesity is the result of white adipose tissue accumulation where excess of food energy is stored to form triglycerides. De novo lipogenesis (DNL) is the continuous process of new fat production and is driven by the transcription factor ChREBP. During adipogenesis, white adipocytes change their morphology and the entire cell volume is occupied by one large lipid droplet. Recent studies have implicated an essential role of autophagy in adipogenic differentiation, cytoplasmic remodelling and mitochondria reorganization. The phenolic monoterpenoid carvacrol (2-methyl-5-[1-methylethyl]phenol), produced by numerous aromatic plants, has been shown to reduce lipid accumulation in murine 3T3-L1 cells during adipogenic differentiation by modulating genes associated with adipogenesis and inflammation. Therefore, the aim of this study was to evaluate whether carvacrol could affect autophagy and ChREBP expression during adipogenic differentiation. The study was carried on by using the murine 3T3-L1 and the human WJ-MSCs (Wharton's jelly-derived mesenchymal stem cells) cell lines. Cells undergoing adipogenic differentiation were untreated or treated with carvacrol. Adipogenic differentiation was assessed by analyzing cellular lipid accumulation with Oil-Red O staining and by ultrastructural examination with TEM. Autophagy was evaluated by western immunoblotting of autophagy markers LC3B and p62/SQSTM and by ultrastructural examination of autophagic bodies. Autophagic flux was evaluated by using autophagy inhibitor cloroquine (CQ). ChREBP expression levels was assessed by both western blotting and immunoelectron microscopy and ChREBP activity by analysis of adipogenic target genes expression. We found that carvacrol reduced adipogenic differentiation of about 40% and 30% in, respectively, 3T3-L1 and in WJ-MSCs cells. The effect of carvacrol on adipogenic differentiation correlated with both reduction of autophagy and reduction of ChREBP expression. The results support the notion that carvacrol, through its effect on autophagy (essential for adipocyte maturation) and on ChREBP activity, could be used as a valuable adjuvant to reduce adipogenic differentiation. Show less