Abstract
Purpose :
It is still a great challenge to deliver therapeutics to the posterior segment of the eye to rescue retinal neurons. Encapsulated cell therapy (ECT) with cellular release of fresh therapeutics enables local sustained drug delivery to the retina while avoiding repeated intravitreal injections. We hypothesized that continuous GDNF secretion by collagen-alginate composite (CAC) ECT device can rescue photoreceptors, finally slowing the progression of retinal degenerative diseases. Here, we fabricated a CAC ECT device and evaluated its 1) safety, biocompatibility, mechanical stability, and in vivo drug delivery and 2) in vivo efficacy to rescue photoreceptors in rabbit eyes.
Methods :
New Zealand White rabbits (N=8) received intravitreal injection of CAC ECT devices. After 2 weeks, safety of CAC ECT device was determined by assessments of IOP and electroretinogram as well as analyses of retinal histology and glial activation. Device biocompatibility and mechanical stability were evaluated by light and scanning electron microscopy (SEM). In vivo GDNF delivery was assayed by ELISA. Rabbits receiving ECT devices (N=4) were also given 0.1mg/ml doxycycline in drinking water for 1 week to examine in vivo termination efficiency. Efficacy of CAC ECT device was investigated in a rabbit model of retinal degeneration (N=7) induced by intravenous injection of sodium iodate (10mg/kg).
Results :
Injected devices were safe and imposed no changes on retinal function and structure. Retrieved devices exhibited good mechanical stability, integrity, no material degradation, and no host tissue attachment with interpenetrating network and living cell colonies. Encapsulated cells were viable and secreted GDNF (p=0.0006). A week of doxycycline treatment could effectively stop the device (p<0.0001). Intravenous sodium iodate induced retinal degeneration with decreased a wave amplitude (p<0.0001), which could be alleviated by CAC ECT device.
Conclusions :
Injected CAC ECT device was mechanically stable, safe, and terminable while viable encapsulated cells secreted GDNF. Most importantly, CAC ECT device restored retinal function in a rabbit model of retinal degeneration, suggesting its potential as a promising drug delivery platform to treat retinal degenerative diseases.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.