RESUMO
Many gastrointestinal motility disorders arise due to defects in the enteric nervous system. Achalasia and gastroparesis are two extremely debilitating digestive diseases of the upper gastrointestinal tract caused in part by damage or loss of the nitrergic neurons in the esophagus and stomach. Most current pharmacological and surgical interventions provide no long-term relief from symptoms, and none address the cause. Stem cell therapy, to replace the missing neurons and restore normal gut motility, is an attractive alternative therapy. However, there are a number of hurdles that must be overcome to bring this exciting research from the bench to the bedside.
Assuntos
Sistema Nervoso Entérico , Gastroenteropatias , Gastroparesia , Humanos , Motilidade Gastrointestinal/fisiologia , Gastroenteropatias/terapia , Gastroparesia/terapia , Terapia Baseada em Transplante de Células e Tecidos , Trato GastrointestinalRESUMO
The retina transforms light into electrical signals, which are sent to the brain via the optic nerve to form our visual perception. This complex signal processing is performed by the retinal neuron and requires a significant amount of energy. Since neurons are unable to store energy, they must obtain glucose and oxygen from the bloodstream to produce energy to match metabolic needs. This process is called neurovascular coupling (NVC), and it is based on a precise mechanism that is not totally understood. The discovery of fine tubular processes termed tunnelling nanotubes (TNTs) set a new type of cell-to-cell communication. TNTs are extensions of the cellular membrane that allow the transfer of material between connected cells. Recently, they have been reported in the brain and retina of living mice, where they connect pericytes, which are vascular mural cells that regulate vessel diameter. Accordingly, these TNTs were termed interpericyte tunnelling nanotubes (IPTNTs), which showed a vital role in blood delivery and NVC. In this chapter, we review the involvement of TNTs in NVC and discuss their implications in retinal neurodegeneration.
Assuntos
Comunicação Celular , Retina , Animais , Humanos , Retina/fisiologia , Comunicação Celular/fisiologia , Pericitos/fisiologia , Nanotubos , Camundongos , Acoplamento Neurovascular/fisiologia , Vasos Retinianos/fisiologia , Estruturas da Membrana CelularRESUMO
Single-cell RNA sequencing (scRNA-seq) has enabled the identification of novel gene signatures and cell heterogeneity in numerous tissues and diseases. Here we review the use of this technology for Fuchs' Endothelial Corneal Dystrophy (FECD). FECD is the most common indication for corneal endothelial transplantation worldwide. FECD is challenging to manage because it is genetically heterogenous, can be autosomal dominant or sporadic, and progress at different rates. Single-cell RNA sequencing has enabled the discovery of several FECD subtypes, each with associated gene signatures, and cell heterogeneity. Current FECD treatments are mainly surgical, with various Rho kinase (ROCK) inhibitors used to promote endothelial cell metabolism and proliferation following surgery. A range of emerging therapies for FECD including cell therapies, gene therapies, tissue engineered scaffolds, and pharmaceuticals are in preclinical and clinical trials. Unlike conventional disease management methods based on clinical presentations and family history, targeting FECD using scRNA-seq based precision-medicine has the potential to pinpoint the disease subtypes, mechanisms, stages, severities, and help clinicians in making the best decision for surgeries and the applications of therapeutics. In this review, we first discuss the feasibility and potential of using scRNA-seq in clinical diagnostics for FECD, highlight advances from the latest clinical treatments and emerging therapies for FECD, integrate scRNA-seq results and clinical notes from our FECD patients and discuss the potential of applying alternative therapies to manage these cases clinically.
RESUMO
Corneal diseases are one of the leading causes of moderate-to-severe visual impairment and blindness worldwide, after glaucoma, cataract, and retinal disease in overall importance. Given its tendency to affect people at a younger age than other blinding conditions such as cataract and glaucoma, corneal scarring poses a huge burden both on the individuals and society. Furthermore, corneal scarring and fibrosis disproportionately affects people in poorer and remote areas, making it a significant ophthalmic public health problem. Traditional medical strategies, such as topical corticosteroids, are not effective in preventing fibrosis or scars. Corneal transplantation, the only effective sight-restoring treatment for corneal scars, is curbed by challenges including a severe shortage of tissue, graft rejection, secondary conditions, cultural barriers, the lack of well-trained surgeons, operating rooms, and well-equipped infrastructures. Thanks to tremendous research efforts, emerging therapeutic options including gene therapy, protein therapy, cell therapy and novel molecules are in development to prevent the progression of corneal scarring and compliment the surgical options currently available for treating established corneal scars in clinics. In this article, we summarise the most relevant preclinical and clinical studies on emerging therapies for corneal scarring in recent years, showing how these approaches may prevent scarring in its early development.