Animal models and drug candidates for use in glaucoma filtration surgery: A systematic review

Ralph J S van Mechelen; Jarno Ej Wolters; Christian J F Bertens; Carroll A B Webers; Frank J H M van den Biggelaar; Theo G M F Gorgels; Henny J M Beckers

doi:10.1016/j.exer.2022.108972

Animal models and drug candidates for use in glaucoma filtration surgery: A systematic review

Exp Eye Res. 2022 Apr:217:108972. doi: 10.1016/j.exer.2022.108972. Epub 2022 Jan 31.

Authors

Ralph J S van Mechelen¹, Jarno Ej Wolters², Christian J F Bertens², Carroll A B Webers³, Frank J H M van den Biggelaar³, Theo G M F Gorgels³, Henny J M Beckers³

Affiliations

¹ University Eye Clinic Maastricht, Maastricht University Medical Center+ (MUMC+), 6202 AZ, Maastricht, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, 6229 ER, Maastricht, the Netherlands; Chemelot Institute for Science and Technology (InSciTe), 6229 GS, Maastricht, the Netherlands. Electronic address: R.vanmechelen@maastrichtuniversity.nl.
² University Eye Clinic Maastricht, Maastricht University Medical Center+ (MUMC+), 6202 AZ, Maastricht, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, 6229 ER, Maastricht, the Netherlands; Chemelot Institute for Science and Technology (InSciTe), 6229 GS, Maastricht, the Netherlands.
³ University Eye Clinic Maastricht, Maastricht University Medical Center+ (MUMC+), 6202 AZ, Maastricht, the Netherlands.

PMID: 35114212
DOI: 10.1016/j.exer.2022.108972

Abstract

Glaucoma, a degenerative disease of the optic nerve, is the leading cause of irreversible blindness worldwide. Currently, there is no curative treatment. The only proven treatment is lowering intraocular pressure (IOP), the most important risk factor. Glaucoma filtration surgery (GFS) can effectively lower IOP. However, approximately 10% of all surgeries fail yearly due to excessive wound healing, leading to fibrosis. GFS animal models are commonly used for the development of novel treatment modalities. The aim of the present review was to provide an overview of available animal models and anti-fibrotic drug candidates. MEDLINE and Embase were systematically searched. Manuscripts until September 1st^, 2021 were included. Studies that used animal models of GFS were included in this review. Additionally, the snowball method was used to identify other publications which had not been identified through the systematic search. Two hundred articles were included in this manuscript. Small rodents (e.g. mice and rats) are often used to study the fibrotic response after GFS and to test drug candidates. Due to their larger eyes, rabbits are better suited to develop medical devices. Novel drugs aim to inhibit specific pathways, e.g. through the use of modulators, monoclonal antibodies, aqueous suppressants or gene therapy. Although most newly studied drugs offer a higher safety profile compared to antimetabolites, their efficacy is in most cases lower when compared to MMC. Current literature on animal models and potential drug candidates for GFS were summarized in this review. Future research should focus on refining current animal models (for example through the induction of glaucoma prior to undertaking GFS) and standardizing animal research to ensure a higher reproducibility and reliability across different research groups. Lastly, novel therapies need to be further optimized, e.g. by conducting more research on the dosage, administration route, application frequency, the option of creating combination therapies, or the development of drug delivery systems for sustained release of anti-fibrotic medication.

Keywords: Animal models; Anti-fibrotic therapy; Drugs; Glaucoma; Glaucoma filtration surgery.

Publication types

Research Support, Non-U.S. Gov't
Review
Systematic Review

MeSH terms

Animals
Fibrosis
Filtering Surgery*
Glaucoma* / drug therapy
Glaucoma* / surgery
Intraocular Pressure
Mice
Mitomycin
Models, Animal
Pharmaceutical Preparations
Rabbits
Rats
Reproducibility of Results

Substances

Pharmaceutical Preparations
Mitomycin