Nanogel-Facilitated In-Situ Delivery of a Cataract Inhibitor.

Dixa Gautam,Devatha P Nair,Michelle G Pedler,Jonathan Mark Petrash

doi:10.3390/biom11081150

Abstract

Cataracts are a leading cause of blindness worldwide. Surgical removal of cataracts is a safe and effective procedure to restore vision. However, a large number of patients later develop vision loss due to regrowth of lens cells and subsequent degradation of the visual axis leading to visual disability. This postsurgical complication, known as posterior capsular opacification (PCO), occurs in up to 30% of cataract patients and has no clinically proven pharmacological means of prevention. Despite the availability of many compounds capable of preventing early steps in PCO development, there is currently no effective means to deliver such therapies into the eye for a suitable duration. To model a solution to this unmet medical need, we fabricated acrylic substrates as intraocular lens (IOL) mimics scaled to place into the capsular bag of the mouse lens following a mock-cataract surgery. Substrates were coated with a hydrophilic crosslinked acrylate nanogel designed to elute Sorbinil, an aldose reductase inhibitor previously shown to suppress PCO. Insertion of the Sorbinil-eluting device into the lens capsule at the time of cataract surgery resulted in substantial prevention of cellular changes associated with PCO development. This model demonstrates that a cataract inhibitor can be delivered into the postsurgical lens capsule at therapeutic levels.

Highlights

Posterior capsule opacification (PCO) is a condition that develops in as many as 50%of cases following surgery for senile cataract, the most common cause of lens opacification [1]
PCO develops from a process of epithelial-to-mesenchymal transition (EMT) of lens epithelial cells left behind after surgical removal of the cataractous lens, either through phacoemulsification or bulk removal of the lens mass mediated by hydrodissection
These results suggest that nanogel-facilitated delivery of therapeutic agents into the postsurgical lens capsule may provide an effective means to delay or prevent development of PCO

Summary

Introduction

Posterior capsule opacification (PCO) is a condition that develops in as many as 50%. Of cases following surgery for senile cataract, the most common cause of lens opacification [1]. PCO develops from a process of epithelial-to-mesenchymal transition (EMT) of lens epithelial cells left behind after surgical removal of the cataractous lens, either through phacoemulsification or bulk removal of the lens mass mediated by hydrodissection. After going through EMT, lens epithelial cells deposit extracellular matrix components that cause contraction, wrinkling of the lens capsule, and interruption of the light path that would otherwise focus on the retina to stimulate photoreceptors. Restoration of a clear light path can be achieved by creating a capsulotomy with use of a Nd:YAG laser. While the YAG procedure is usually successful and uneventful, eyes with such capsulotomies are at higher risk for retinal detachment, cystoid macular edema, and increased ocular pressures [2].

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