Emerging Gene Therapy Technologies for Retinal Ganglion Cell Neuroprotection.

ABSTRACT: Optic neuropathies encompass a breadth of diseases that ultimately result in dysfunction and/or loss of retinal ganglion cells (RGCs). Although visual impairment from optic neuropathies is common, there is a lack of effective clinical treatments. Addressing a critical need for novel interventions, preclinical studies have been generating a growing body of evidence that identify promising new drug-based and cell-based therapies. Gene therapy is another emerging therapeutic field that offers the potential of specifically and robustly increasing long-term RGC survival in optic neuropathies. Gene therapy offers additional benefits of driving improvements following a single treatment administration, and it can be designed to target a variety of pathways that may be involved in individual optic neuropathies or across multiple etiologies. This review explores the history of gene therapy, the fundamentals of its application, and the emerging development of gene therapy technology as it relates to treatment of optic neuropathies.

Vagal nerve stimulation attenuates IL-6 and TNFα expression in respiratory regions of the developing rat brainstem.

Pre-term infants are at greater risk for systemic infection due to an underdeveloped immune system. Airway infection results in immune up-regulation of early pro-inflammatory cytokines interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) in the brainstem. Current treatment for neonatal infection involves antibiotic administration. We previously showed that LPS injected into the trachea of neonatal rats causes changes in breathing and in IL-1ß expression in the nucleus tractus solitarii (NTS) and hypoglossal motor nucleus (XII). We hypothesize that lipopolysaccharide (LPS) instilled in the trachea also causes the up-regulation of IL-6 and TNFα in the brainstem autonomic control regions. To test this hypothesis we injected LPS into the trachea of rat pups (postnatal ages 10-12days) and then assessed changes in IL-6 and TNFα. Vagal nerve stimulation has been used in the treatment of many inflammatory disorders, including sepsis. Our experiments show that VNS attenuates the upregulation of IL-6 and TNFα caused by LPS and may be a viable alternative to antibiotics.