Eye drop that reaches posterior ocular tissues could protect retinal cells

Reviewed by Dr Laura Ensign.

A novel eye drop in preclinical development may provide neuroprotection to the retinal ganglion cells (RGCs). An added plus is that only once-weekly dosing is required, according to Dr Laura Ensign, who headed the research. Dr Ensign holds the Marcella E. Woll Professorship in Ophthalmology and is an associate professor of ophthalmology and vice chair for research at the Wilmer Eye Institute, Johns Hopkins Medicine in Baltimore, Maryland, United States.

This work is being conducted in collaboration with Dr Justin Hanes, who is the Lewis J. Ort Professor of Ophthalmology and director of the Center for Nanomedicine at the Johns Hopkins University School of Medicine, and Dr Donald J. Zack, the Guerrieri Professor of Genetic Engineering and Molecular Ophthalmology and co-director of the Center for Stem Cells and Ocular Regenerative Medicine at the Wilmer Eye Institute.

The need to protect RGCs during treatment

Anti-glaucoma eye drops are the mainstay of treatment for the disease, and they successfully and significantly lower intraocular pressure (IOP). However, despite the drops achieving this reduction in IOP, degeneration of RGCs in the retina may progress, threatening vision in many patients. A therapy that protects the RGCs from damage was just a dream until the advent of this novel approach.

“The concept of delivering a drug to protect RGCs is not something that is currently done clinically, but as a complement to IOP lowering, may be an important glaucoma management tool,” Dr Ensign said. “The fact that we can potentially protect the RGCs using an eye drop is unique and interesting, because this route is not typically used to deliver therapy to the retina.” The investigators reported their progress in Drug Delivery and Translational Research.¹

The innovation

The path that eye drops take to reach posterior ocular tissues of the eye. (Image courtesy of Dr Laura Ensign, PhD)

The novel gel-forming eye drop contains the drug sunitinib (Sutent, Pfizer), a protein kinase inhibitor used to treat cancer. After being delivered, it remains in place for an extended period and provides increased intraocular drug absorption.

In combination with the intrinsic melanin-binding properties of sunitinib, drug binding in the pigmented cells in the choroid and retinal pigment epithelium provided sustained, therapeutically relevant drug concentrations in the retina to protect the RGCs. “The process of binding to melanin serves as a reservoir for the drug – i.e., it is a built-in sustained delivery system in the ocular cells,” Dr Ensign said.

The two-fold advantages of this therapeutic pathway are clear: firstly, transport of the drug to the back of the eye in sufficiently high therapeutic concentrations, and secondly, the sustained release of the drug over time from melanin. The investigators found that this capability allowed for once-weekly dosing that continued to provide a therapeutic effect in the retina, which has the potential to decrease the patient treatment burden.

Moving the research along

Dr Ensign and Dr Hanes have formed a start-up company under the umbrella of Johns Hopkins to develop the eye drop technology. They are currently considering the potential of moving the eye drop into clinical trials. The ultimate goal is to have an eye drop available in a few years that is intended to treat retinal disease, according to Dr Ensign.

In a previous publication,² Dr Ensign and her colleagues—in collaboration with Dr Peter Campochiaro, also from the Wilmer Eye Institute—used a porcine model to show that choroidal neovascularisation was prevented by the sunitinib gel-forming eye drop, in contrast to a saline eye drop version of the drug, which had no effect. “Our eye drop decreased the area of neovascularisation by [approximately] half,” Dr Ensign said.

The next step is to evaluate the effect of different doses of the sunitinib drop for glaucoma. In addition, for age-related macular degeneration, the investigators are considering a daily dose.

Laura Ensign, PhD

E: lensign@jhmi.edu

Dr Ensign has a financial interest in this technology. She is one of the inventors listed on patents/patent applications related to this technology and is one of the co-founders of the start-up company planning to develop the eye drop technology for clinical use.

References

1. Kim YC, Hsueh HT, Shin MD, et al. A hypotonic gel-forming eye drop provides enhanced intraocular delivery of a kinase inhibitor with melanin-binding properties for sustained protection of retinal ganglion cells. Drug Deliv Transl Res. 2022;12:826-837.

2. Kim YC, Shin MD, Hackett SF, et al. Gelling hypotonic polymer solution for extended topical drug delivery to the eye. Nature Biomed Eng. 2020;4:1053-1062.