No abstract

Visual impairment and blindness are a growing public health problem, as they reduce the quality of life of millions of people. The management and treatment of these diseases represent a scientific and therapeutic challenge, since the different cellular and molecular actors involved in the pathophysiology are still being identified. The visual system components, particularly the retinal cells, are extremely sensitive to genetic or metabolic alterations, and immune cells activated by insults contribute to biological events that culminate with vision loss and irreversible blindness. Several ocular diseases are linked to retinal cell loss, and diseases such as retinitis pigmentosa, age-related macular degeneration, glaucoma and diabetic retinopathy are characterized by pathophysiological hallmarks that represent possibilities to study and develop novel treatments for retinal cells degeneration. Here, we present a compilation of revisited information on retinal degeneration, including pathophysiologic and molecular features, biochemical hallmarks and possible directions for novel treatments, aiming to assist as a guide for innovative research. The expansion of knowledge of the mechanistic bases of the pathobiology of eye diseases, including information on the complex interactions of genetic predisposition, chronic inflammation, and environmental and aging-related factors will allow the identification of new therapeutic strategies.

Asthma is the most common chronic lung disease, with increasing morbidity and mortality worldwide. Accumulation of peribronchial leukocytes is the hallmark of asthma, in particular, eosinophils, which have been reported as the primary cell associated with the induction of airway hyperresponsiveness. Continued exacerbation and accumulation of other leukocytes, such as neutrophils, Th1, and Th17 cells correlate with many of the long-term effects of asthma, such as airway remodeling. We have patented the TnP family of synthetic cyclic peptides, which is in the preclinical phase of developmental studies for chronic inflammatory diseases. The aim of this work was to investigate whether TnP could show anti-inflammatory activity in a murine model of asthma that includes a mixed phenotype of eosinophilic and neutrophilic inflammation. For this, Balb/c mice, sensitized with OVA and exposed to 1% challenge with OVA aerosol, were submitted to prophylactic treatment, receiving TnP at 0.3 mg/kg orally, 1 h before each challenge. We found that sensitized mice challenged with OVA and treated with TnP showed no airway hyperreactivity or lung remodeling. TnP acts systemically in secondary lymphoid organs and locally in the lung, inhibiting the production of Th2/Th17 cytokines. Furthermore, TnP prevented the infiltration of eosinophils and neutrophils in the BAL and lung tissue, inhibited the production of IgE/IgG1, prevented hyperplasia of mucus-producing cells, and decreased the thickening and deposition of sub-epithelial collagen. Our results showed TnP as a candidate molecule for the treatment of airway remodeling associated with inflammatory diseases, such as asthma.