TY - JOUR
T1 - Animal models and drug candidates for use in glaucoma filtration surgery
T2 - A systematic review
AU - van Mechelen, Ralph J S
AU - Wolters, Jarno Ej
AU - Bertens, Christian J F
AU - Webers, Carroll A B
AU - van den Biggelaar, Frank J H M
AU - Gorgels, Theo G M F
AU - Beckers, Henny J M
N1 - Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.
PY - 2022/4
Y1 - 2022/4
N2 - 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.
AB - 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.
KW - Animal models
KW - Anti-fibrotic therapy
KW - CONJUNCTIVAL FIBROSIS
KW - Drugs
KW - FILTERING SURGERY
KW - GENE-THERAPY
KW - Glaucoma
KW - Glaucoma filtration surgery
KW - IN-VIVO
KW - MITOMYCIN-C
KW - RABBIT MODEL
KW - SCAR FORMATION
KW - SURGICAL-TREATMENT
KW - TISSUE GROWTH-FACTOR
KW - WOUND-HEALING MODULATION
U2 - 10.1016/j.exer.2022.108972
DO - 10.1016/j.exer.2022.108972
M3 - (Systematic) Review article
C2 - 35114212
SN - 0014-4835
VL - 217
JO - Experimental Eye Research
JF - Experimental Eye Research
M1 - 108972
ER -