Application of Canaloplasty in Glaucoma Gene Therapy: Where Are We?

Abstract

Purpose: Schlemm's canal (SC) inner wall is adjacent to the juxtacanalicular trabecular meshwork (TM) over their entire circumference. We seek to transfer reporter and therapeutic genes to these outflow-modulating tissues via canaloplasty surgery in live monkeys. Methods: A standard canaloplasty surgical approach was performed in cynomolgus monkeys using flexible canaloplasty catheters, modified for monkey eyes with a 175-mm outer diameter and an LED-lighted tip. A 6-0 prolene suture was used for the exact localization of SC. Trypan blue was injected during catheter withdrawal to document catheter placement within SC and to determine ease of injecting fluid into SC. Before, during, and after the injection, the position of the catheter and the anatomic details were video-captured with an externally positioned noncontact endoscopic imaging system and 50 mHz ultrasound biomicroscopy (UBM). Results: A 360°catheterization and injection of dye into SC was achieved. Suture, catheter, and trypan blue were imaged with the endoscope camera system and the catheter was also visualized with UBM. Trypan blue was seen in the SC over 5 clock hours after a 1 clock-hour insertion of the catheter. Conclusions: A modified canaloplasty catheter device might be used for gene delivery to the SC/TM area without circumferential catheterization. Further studies comparing different delivery methods of the vector/ transgene into the SC using canaloplasty are needed.

Aqueous Humor Outflow Structure and Function Imaging At the Bench and Bedside: A Review

“…Channelography and canalography are essentially the same technique that relies on unroofing Schlemm’s canal (SC) with introduction of the tracer (fluorescein, ICG, or trypan blue) [54–59]. The introduction can occur through local injection analogous to a viscocanulostomy surgery or through intermittent deposition from a flexible microcatheter as it is pulled through the eye during canaloplasty surgery.…”

MicroRNA-93 is overexpressed and induces apoptosis in glaucoma trabecular meshwork cells

“…These specific expression profiles may provide tools for cell isolation, target gene modulation in specific stages and cell types, and gene therapy (32). As for glaucoma, gene therapy is promising owing to the modification and improvement of transgene vector delivery methods, including canaloplasty, which are under investigation (33,34). Further investigations on the therapeutic targets of glaucoma are essential for the future implementation of gene therapy for glaucoma.…”

Structural and functional imaging of aqueous humour outflow: a review

“…Canaloplasty was described above in the structural analyses of conventional (trabecular) AHO. In canalograms, after SC exposure, tracers could either be directly injected into SC with image acquisition in live subjects or during the reversal step when the canaloplasty probe was backed out of the eye to suture thread SC . While backing out, dollops of tracer (normally viscoelastic to achieve a viscodilation) could be dropped to visualize AHO pathways.…”

“…Canalograms yielded excellent images showing outflow around the limbus. [52][53][54][55] However, by introducing the tracer into SC, the contribution of TM to outflow was not included, and this was not physiologic. Also, segmentalization was harder to appreciate.…”