Association of Circulating Antiretinal Antibodies With Clinical Outcomes in Retinitis Pigmentosa.

Purpose: To determine if circulating antiretinal antibodies (ARAs) differ between patients affected by retinitis pigmentosa (RP) and control participants and to assess whether ARAs are associated with clinical outcomes in patients with RP. Methods: Cross-sectional study involving a group of patients clinically diagnosed with RP and a control group of healthy participants. Serum autoantibodies against enolase, heat shock protein 70 (HSP70), and carbonic anhydrase II (CAII) were tested in all participants using Jess capillary Western blot. We compared ARA prevalence between the RP and control groups and investigated the association of serum ARA positivity with macular edema and vitreomacular disorders in patients affected by RP. Results: Thirty-six patients affected by RP and a control group of 39 healthy individuals were included. Overall, at least one ARA positivity was detected in 89% and 80% of participants in the RP and control groups, respectively. We observed a similar prevalence of anti-CAII and anti-enolase ARA between patients and controls (P = 0.87 and P = 0.35, respectively). Sera from patients with RP tested positive for anti-HSP70 ARAs more frequently than those from controls (53% vs. 36%), albeit without reaching statistical significance (P = 0.29). Among the 72 eyes with RP, 25% presented with macular edema (most often bilateral) and 33% with epiretinal membrane and/or lamellar macular hole. None of the three ARAs was associated with an increased risk of any macular complications in eyes affected by RP (all P > 0.05). Conclusions: The prevalence of circulating ARAs against enolase, HSP70, and CAII is similar between patients affected by RP and healthy individuals. Our results provide evidence against the association of ARAs with macular edema and vitreomacular interface disorders in RP.

Inhibition of class I HDACs imprints adipogenesis toward oxidative and brown-like phenotype.

Obesity is characterized by uncontrolled expansion of adipose tissue mass, resulting in adipocyte hypertrophy (increased adipocyte size) and hyperplasia (increased number of adipocytes). The number of adipose cells is directly related to adipocyte differentiation process from stromal vascular cells to mature adipocytes. It is known that epigenetic factors influence adipose differentiation program. However, how specific epigenome modifiers affect white adipocyte differentiation and metabolic phenotype is still matter of research. Here, we provide evidence that class I histone deacetylases (HDACs) are involved both in the differentiation of adipocytes and in determining the metabolic features of these cells. We demonstrate that inhibition of class I HDACs from the very first stage of differentiation amplifies the differentiation process and imprints cells toward a highly oxidative phenotype. These effects are related to the capacity of the inhibitor to modulate H3K27 acetylation on enhancer regions regulating Pparg and Ucp1 genes. These epigenomic modifications result in improved white adipocyte functionality and metabolism and induce browning. Collectively, our results show that modulation of class I HDAC activity regulates the metabolic phenotype of white adipocytes via epigenetic imprinting on a key histone mark.

Ketogenic Diet: A New Light Shining on Old but Gold Biochemistry.

Diets low in carbohydrates and proteins and enriched in fat stimulate the hepatic synthesis of ketone bodies (KB). These molecules are used as alternative fuel for energy production in target tissues. The synthesis and utilization of KB are tightly regulated both at transcriptional and hormonal levels. The nuclear receptor peroxisome proliferator activated receptor α (PPARα), currently recognized as one of the master regulators of ketogenesis, integrates nutritional signals to the activation of transcriptional networks regulating fatty acid ß-oxidation and ketogenesis. New factors, such as circadian rhythms and paracrine signals, are emerging as important aspects of this metabolic regulation. However, KB are currently considered not only as energy substrates but also as signaling molecules. ß-hydroxybutyrate has been identified as class I histone deacetylase inhibitor, thus establishing a connection between products of hepatic lipid metabolism and epigenetics. Ketogenic diets (KD) are currently used to treat different forms of infantile epilepsy, also caused by genetic defects such as Glut1 and Pyruvate Dehydrogenase Deficiency Syndromes. However, several researchers are now focusing on the possibility to use KD in other diseases, such as cancer, neurological and metabolic disorders. Nonetheless, clear-cut evidence of the efficacy of KD in other disorders remains to be provided in order to suggest the adoption of such diets to metabolic-related pathologies.