Post-Vitrectomy Endophthalmitis in Victoria, Australia

Abstract

Treatment of diseases with gene therapy is advancing rapidly. The use of gene therapy has expanded from the original concept of replacing the mutated gene causing the disease to the use of genes to control nonphysiological levels of expression or to modify pathways known to affect the disease. Genes offer numerous advantages over conventional drugs. They have longer duration of action and are more specific. Genes can be delivered to the target site by naked DNA, cells, nonviral, and viral vectors. The enormous progress of the past decade in molecular biology and delivery systems has provided ways for targeting genes to the intended cell/tissue and safe, long-term vectors. The eye is an ideal organ for gene therapy. It is easily accessible and it is an immune-privileged site. Currently, there are clinical trials for diseases affecting practically every tissue of the eye, including those to restore vision in patients with Leber congenital amaurosis. However, the number of eye trials compared with those for systemic diseases is quite low (1.8%). Nevertheless, judging by the vast amount of ongoing preclinical studies, it is expected that such number will increase considerably in the near future. One area of great need for eye gene therapy is glaucoma, where a long-term gene drug would eliminate daily applications and compliance issues. Here, we review the current state of gene therapy for glaucoma and the possibilities for treating the trabecular meshwork to lower intraocular pressure and the retinal ganglion cells to protect them from neurodegeneration.

Transduction Pattern of AAVs in the Trabecular Meshwork and Anterior-Segment Structures in a Rat Model of Ocular Hypertension

“…Furthermore, the magnitude of scAAV5 transduction in the TM and Schlemm’s canal was greater than that of the other serotypes. In contrast, in cultured human and porcine TM cells, the transduction efficiency of scAAV5 was greater than that of scAAV2; thus, scAAV tropism may differ among species 25 . However, no study has evaluated recombinant AAV8 or scAAV8 transduction in anterior-segment structures.…”

“…reported that intracameral injection of scAAV2-GFP resulted in persistent gene expression in the TM for more than 2 years. Also, transduction of scAAV2 has been demonstrated in primary human TM and porcine-perfused organ cultures 25 . Intracameral injection of scAAV5 in live rats resulted in greater transduction in the TM than did scAAV2 25 .…”

“…Also, transduction of scAAV2 has been demonstrated in primary human TM and porcine-perfused organ cultures 25 . Intracameral injection of scAAV5 in live rats resulted in greater transduction in the TM than did scAAV2 25 . Furthermore, the magnitude of scAAV5 transduction in the TM and Schlemm’s canal was greater than that of the other serotypes.…”

The effects of PEGylation on LNP based mRNA delivery to the eye

“…The TM is most likely transduced as the particles get circulated out of the vitreous chamber. The TM and the ONH are commonly under investigation to better understand and treat glaucoma [36][37][38]. Specific to the TM, researchers have been investigating and developing gene therapy approaches that reduce ocular pressure [37].…”

“…The TM and the ONH are commonly under investigation to better understand and treat glaucoma [36][37][38]. Specific to the TM, researchers have been investigating and developing gene therapy approaches that reduce ocular pressure [37]. As glaucoma is a multifaceted disease, researchers have also developed a method of small molecule delivery to the ONH of rats that allows for exploration of molecular and cellular pathways involved in neuropathies and treatment screening [38].…”