June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Long-term oral treatment with low dose glibenclamide reduces diabetic retinopathy damage in the Goto-Kakizaki rat model
Author Affiliations & Notes
  • Marianne Berdugo-Polak
    Université de Paris, Faculté de santé, Centre de Recherche des Cordeliers, Universite de Paris, Paris, Île-de-France, France
  • kimberley delaunay
    Inserm UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, INSERM, Paris, Île-de-France, France
  • Marie-Christine Naud
    Inserm UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, INSERM, Paris, Île-de-France, France
  • Lolita Radet
    Université de Paris, Faculté de santé, Centre de Recherche des Cordeliers, Universite de Paris, Paris, Île-de-France, France
  • Emmanuelle Gelizé
    Inserm UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, INSERM, Paris, Île-de-France, France
  • Simon Perreau
    Université de Paris, Faculté de santé, Centre de Recherche des Cordeliers, Universite de Paris, Paris, Île-de-France, France
  • Laurent Jonet
    Inserm UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, INSERM, Paris, Île-de-France, France
  • Dalen Rosa
    Wesleyan University, Middletown, Connecticut, United States
  • Théo Guyon
    Université de Paris, Faculté de santé, Centre de Recherche des Cordeliers, Universite de Paris, Paris, Île-de-France, France
    Inserm UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, INSERM, Paris, Île-de-France, France
  • Emilie Picard
    Inserm UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, INSERM, Paris, Île-de-France, France
  • Alejandra Daruich
    Université de Paris, Faculté de santé, Centre de Recherche des Cordeliers, Universite de Paris, Paris, Île-de-France, France
    Hopital Necker-Enfants Malades, Department of Ophthalmology, Hopital universitaire Necker-Enfants malades, Paris, Île-de-France, France
  • Jacques Beltrand
    Université de Paris, Faculté de santé, Centre de Recherche des Cordeliers, Universite de Paris, Paris, Île-de-France, France
    Hôpital Necker-Enfants Malades, Department of paediatric endocrinology, gynecology and diabetology, Hopital universitaire Necker-Enfants malades, Paris, Île-de-France, France
  • Elsa Kermorvant-Duchemin
    Université de Paris, Faculté de santé, Centre de Recherche des Cordeliers, Universite de Paris, Paris, Île-de-France, France
    Hopital Necker-Enfants Malades, Department of neonatology, Hopital universitaire Necker-Enfants malades, Paris, Île-de-France, France
  • Michel Polak
    Université de Paris, Faculté de santé, Centre de Recherche des Cordeliers, Universite de Paris, Paris, Île-de-France, France
    Hôpital Necker-Enfants Malades, Department of paediatric endocrinology, gynecology and diabetology, Hopital universitaire Necker-Enfants malades, Paris, Île-de-France, France
  • Patricia Crisanti
    Inserm UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, INSERM, Paris, Île-de-France, France
  • Francine F Behar-Cohen
    Université de Paris, Faculté de santé, Centre de Recherche des Cordeliers, Universite de Paris, Paris, Île-de-France, France
    Inserm UMRS 1138, Centre de Recherche des Cordeliers, Sorbonne Université, Université de Paris, INSERM, Paris, Île-de-France, France
  • Footnotes
    Commercial Relationships   Marianne Berdugo-Polak, None; kimberley delaunay, None; Marie-Christine Naud, None; Lolita Radet, None; Emmanuelle Gelizé, None; Simon Perreau, None; Laurent Jonet, None; Dalen Rosa, None; Théo Guyon, None; Emilie Picard, None; Alejandra Daruich, None; Jacques Beltrand, None; Elsa Kermorvant-Duchemin, None; Michel Polak, Ammtek (C), Nordic Pharma (C); Patricia Crisanti, None; Francine Behar-Cohen, None
  • Footnotes
    Support  French Fondation de France, the association Centre de Recherche en Ophtalmologie (CRO)-Tous unis pour la Vision, the Aide aux Jeunes Diabétiques, the Société Francophone du Diabète, the French Agence Nationale de la Recherche (ANR-15-CE18-0032)
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 1092. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Marianne Berdugo-Polak, kimberley delaunay, Marie-Christine Naud, Lolita Radet, Emmanuelle Gelizé, Simon Perreau, Laurent Jonet, Dalen Rosa, Théo Guyon, Emilie Picard, Alejandra Daruich, Jacques Beltrand, Elsa Kermorvant-Duchemin, Michel Polak, Patricia Crisanti, Francine F Behar-Cohen; Long-term oral treatment with low dose glibenclamide reduces diabetic retinopathy damage in the Goto-Kakizaki rat model. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1092.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Glibenclamide (Glyburide), a Sulfonylurea drug used to lower blood glucose in diabetic patients, was shown to be neuroprotective when administered either systemically or locally in rat models of hyperglycemia or excitotoxicity-induced retinal degeneration. Its administration, at non-hypoglycemic doses, protected retinal function and structure. It acts through its binding to the Sulfonylurea receptor SUR1, extensively expressed in rodent, monkey and human neuroretinas (Berdugo et al. 2020). In this study, we investigated the protective effects of life-long oral treatment with glibenclamide, at low dose, in the Goto-Kakizaki (GK) rat model of diabetic retinopathy (DR).

Methods : GK rats were force-fed with a glibenclamide oral suspension (Amglidia(ND), Ammtek/Nordic Pharma) or vehicle twice a day, 5d/wk, from 2-months (hyperglycemia onset) to 12-months of age (previouslyly described stage of DR; Omri S, 2013; Rothschild PR, 2017). At 12 months, we measured neuroretinal thickness on Optical Coherence Tomography (OCT) pictures, we quantified retinal vascularisation and vascular diameters on fluorescent lectin-labeled neuroretinal flatmounts, photographed with a confocal microscope and using a self-made ImageJ macro. We evaluated retinal function evolution through electroretinography testing (ERG) in glibenclamide vs. vehicle treated diabetic animals and vs. non-diabetic Wistar rats (WS).

Results : Diabetes induced retinal thickening on OCT pictures (mean 337±3.7 sem vs. 303±3.8 microns) and treatment reduced this thickening (315±4.5 microns P<0.05). The proportion of retinal capillaries is increased by 7.8% in the treated group compared to vehicle-treated group (P=0.04). ERG parameters reflecting the inner retina activity were damaged at 12 months in GK rats compared to WS rats (first scotopic oscillatory potential implicit time=33.5±0.3 vs. 30.4±0.26 ms, P=0.0001, n=15 and 8) and partially protected in treated animals (32.4±0.29 ms, P=0.03, n=7).

Conclusions : Long-term low-dose oral glibenclamide treatment partially prevents RD vascular, edematous and functional damage in diabetic GK rats. As the oral drug is already available for patients, we are now exploring incidence and severity of DR in patients treated by glibenclamide vs. other medications, and developing a local formulation for ocular diseases.

This is a 2021 ARVO Annual Meeting abstract.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×