The eye is at the forefront of the application of gene therapy techniques to medicine. In the United States, a gene therapy treatment for Leber's congenital amaurosis, a rare inherited retinal disease, recently became the first gene therapy to be approved by the FDA for the treatment of disease caused by mutations in a specific gene. Phase III clinical trials of gene therapy for other single-gene defect diseases of the retina and optic nerve are also currently underway. However, for optic nerve diseases not caused by single-gene defects, gene therapy strategies are likely to focus on slowing or preventing neuronal death through the expression of neuroprotective agents. In addition to these strategies, there has also been recent interest in the potential use of precise genome editing techniques to treat ocular disease. This review focuses on recent developments in gene therapy techniques for the treatment of glaucoma and Leber's hereditary optic neuropathy (LHON). We discuss recent successes in clinical trials for the treatment of LHON using gene supplementation therapy, promising neuroprotective strategies that have been employed in animal models of glaucoma and the potential use of genome editing techniques in treating optic nerve disease.

Legged locomotion in terrestrial animals is often essential for mating and survival, and locomotor behavior must be robust and adaptable to be successful. This adaptability is largely provided by proprioceptors monitoring positions and movements of body parts and providing feedback to other components of locomotor networks. In insects, proprioceptive chordotonal organs span joints and encode parameters of relative movement between segments. Previous studies have used whole-organ ablation, reduced preparations, or broad physiological manipulations to impair the function of the femoral chordotonal organ (fCO), which monitors the femur-tibia joint, and have demonstrated its contribution to interleg coordination and walking behavior. The fCO in Drosophila melanogaster comprises groups of neurons that differ in their morphology and encoding properties (club, hook, claw); sub-population-level manipulations of fCO function have not been methodologically accessible. Here, we take advantage of the genetic toolkit available in D. melanogaster to identify sub-populations of fCO neurons and use transient optogenetic inhibition to investigate their roles in locomotor coordination. Our findings demonstrate that optogenetic inhibition of a subset of club and hook neurons replicates the effects of inhibiting the whole fCO; when inhibited alone, however, the individual subset types did not strongly affect spatial aspects of single-leg kinematics. Moreover, fCO subsets seem to play only a minor role in interleg temporal coordination. Thus, the fCO contains functionally distinct subgroups, and this functional classification may differ from those based on anatomy and encoding properties; this should be investigated in future studies of proprioceptors and their involvement in locomotor networks.

Background Small cell carcinoma is a highly aggressive and often fatal cancer that most commonly arises in the lung, although it can occasionally arise from other sites, such as the gastrointestinal tract, prostate or cervix. Cardiac involvement, however, is extremely uncommon and therefore has been poorly documented in the literature. Case presentation We describe a rare case of a 31-year-old male with small cell carcinoma presenting as a massive, 15-cm cardiac tumor invading the bilateral atria, interatrial septum, and pericardium without an apparent primary malignancy on PET CT and cardiac MRI. With extensive tissue necrosis, traditional methods of obtaining a right atrial endomyocardial biopsy via internal jugular venous access failed and a diagnosis was made via endoscopic ultrasound guided transesophageal fine needle aspiration of the left atrial mass. Due to the extensive tumor invasion, the patient was not a suitable candidate for surgical resection, debulking, or heart transplant. The patient was treated with etoposide, carboplatin, atezolizumab, and radiation therapy with initial monitoring in the intensive care unit due to concern that tumor lysis may cause rapid cardiac decompensation. Unfortunately, 4 months after chemoradiation therapy, the malignancy progressed and the patient passed away 6 months after the initial diagnosis. Conclusion We describe a rare occurrence of small cell carcinoma presenting as a massive cardiac tumor without apparent primary malignancy. This case demonstrates useful alternative diagnostic strategies and treatment considerations for patients presenting with a rare cardiac mass.

No abstract