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Targeting RGD-binding integrins as an integrative therapy for diabetic retinopathy and neovascular age-related macular degeneration.
Prog Retin Eye Res. 2021 Mar 26 [Online ahead of print]PR

Abstract

Integrins are a class of transmembrane receptors that are involved in a wide range of biological functions. Dysregulation of integrins has been implicated in many pathological processes and consequently, they are attractive therapeutic targets. In the ophthalmology arena, there is extensive evidence suggesting that integrins play an important role in diabetic retinopathy (DR), age-related macular degeneration (AMD), glaucoma, dry eye disease and retinal vein occlusion. For example, there is extensive evidence that arginyl-glycyl-aspartic acid (Arg-Gly-Asp; RGD)-binding integrins are involved in key disease hallmarks of DR and neovascular AMD (nvAMD), specifically inflammation, vascular leakage, angiogenesis and fibrosis. Based on such evidence, drugs that engage integrin-linked pathways have received attention for their potential to block all these vision-threatening pathways. This review focuses on the pathophysiological role that RGD-binding integrins can have in complex multifactorial retinal disorders like DR, diabetic macular edema (DME) and nvAMD, which are leading causes of blindness in developed countries. Special emphasis will be given on how RGD-binding integrins can modulate the intricate molecular pathways and regulate the underlying pathological mechanisms. For instance, the interplay between integrins and key molecular players such as growth factors, cytokines and enzymes will be summarized. In addition, recent clinical advances linked to targeting RGD-binding integrins in the context of DME and nvAMD will be discussed alongside future potential for limiting progression of these diseases.

Authors+Show Affiliations

Oxurion NV, Gaston Geenslaan 1, 3001, Heverlee, Belgium. Electronic address: Inge.VanHove@oxurion.com.Oxurion NV, Gaston Geenslaan 1, 3001, Heverlee, Belgium. Electronic address: Tjing-Tjing.Hu@oxurion.com.Oxurion NV, Gaston Geenslaan 1, 3001, Heverlee, Belgium. Electronic address: Karen.Beets@oxurion.com.Oxurion NV, Gaston Geenslaan 1, 3001, Heverlee, Belgium. Electronic address: Tine.VanBergen@oxurion.com.Oxurion NV, Gaston Geenslaan 1, 3001, Heverlee, Belgium. Electronic address: Isabelle.Etienne@oxurion.com.Oxurion NV, Gaston Geenslaan 1, 3001, Heverlee, Belgium; Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Northern Ireland, UK. Electronic address: a.stitt@qub.ac.uk.Oxurion NV, Gaston Geenslaan 1, 3001, Heverlee, Belgium. Electronic address: Elke.Vermassen@oxurion.com.Oxurion NV, Gaston Geenslaan 1, 3001, Heverlee, Belgium. Electronic address: Jean.Feyen@oxurion.com.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

33775825

Citation

Van Hove, Inge, et al. "Targeting RGD-binding Integrins as an Integrative Therapy for Diabetic Retinopathy and Neovascular Age-related Macular Degeneration." Progress in Retinal and Eye Research, 2021, p. 100966.
Van Hove I, Hu TT, Beets K, et al. Targeting RGD-binding integrins as an integrative therapy for diabetic retinopathy and neovascular age-related macular degeneration. Prog Retin Eye Res. 2021.
Van Hove, I., Hu, T. T., Beets, K., Van Bergen, T., Etienne, I., Stitt, A. W., Vermassen, E., & Feyen, J. H. M. (2021). Targeting RGD-binding integrins as an integrative therapy for diabetic retinopathy and neovascular age-related macular degeneration. Progress in Retinal and Eye Research, 100966. https://doi.org/10.1016/j.preteyeres.2021.100966
Van Hove I, et al. Targeting RGD-binding Integrins as an Integrative Therapy for Diabetic Retinopathy and Neovascular Age-related Macular Degeneration. Prog Retin Eye Res. 2021 Mar 26;100966. PubMed PMID: 33775825.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Targeting RGD-binding integrins as an integrative therapy for diabetic retinopathy and neovascular age-related macular degeneration. AU - Van Hove,Inge, AU - Hu,Tjing-Tjing, AU - Beets,Karen, AU - Van Bergen,Tine, AU - Etienne,Isabelle, AU - Stitt,Alan W, AU - Vermassen,Elke, AU - Feyen,Jean H M, Y1 - 2021/03/26/ PY - 2021/01/08/received PY - 2021/03/15/revised PY - 2021/03/19/accepted PY - 2021/3/30/pubmed PY - 2021/3/30/medline PY - 2021/3/29/entrez KW - Diabetic retinopathy KW - Neovascular age-related macular degeneration KW - RGD-binding integrin KW - Retina SP - 100966 EP - 100966 JF - Progress in retinal and eye research JO - Prog Retin Eye Res N2 - Integrins are a class of transmembrane receptors that are involved in a wide range of biological functions. Dysregulation of integrins has been implicated in many pathological processes and consequently, they are attractive therapeutic targets. In the ophthalmology arena, there is extensive evidence suggesting that integrins play an important role in diabetic retinopathy (DR), age-related macular degeneration (AMD), glaucoma, dry eye disease and retinal vein occlusion. For example, there is extensive evidence that arginyl-glycyl-aspartic acid (Arg-Gly-Asp; RGD)-binding integrins are involved in key disease hallmarks of DR and neovascular AMD (nvAMD), specifically inflammation, vascular leakage, angiogenesis and fibrosis. Based on such evidence, drugs that engage integrin-linked pathways have received attention for their potential to block all these vision-threatening pathways. This review focuses on the pathophysiological role that RGD-binding integrins can have in complex multifactorial retinal disorders like DR, diabetic macular edema (DME) and nvAMD, which are leading causes of blindness in developed countries. Special emphasis will be given on how RGD-binding integrins can modulate the intricate molecular pathways and regulate the underlying pathological mechanisms. For instance, the interplay between integrins and key molecular players such as growth factors, cytokines and enzymes will be summarized. In addition, recent clinical advances linked to targeting RGD-binding integrins in the context of DME and nvAMD will be discussed alongside future potential for limiting progression of these diseases. SN - 1873-1635 UR - https://www.unboundmedicine.com/medline/citation/33775825/Targeting_RGD-binding_integrins_as_an_integrative_therapy_for_diabetic_retinopathy_and_neovascular_age-related_macular_degeneration. L2 - https://linkinghub.elsevier.com/retrieve/pii/S1350-9462(21)00027-6 DB - PRIME DP - Unbound Medicine ER -
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