June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Novel GLP-1 secretagogues as neuroprotective agents for retinal neurodegenerative diseases
Author Affiliations & Notes
  • Folami Lamoke Powell
    Biochemistry and Molecular Biology, Medical College of Georgia at Augusta University, Augusta, Georgia, United States
  • Shakera Thomas
    Morehouse School of Medicine, Atlanta, Georgia, United States
  • Pamela M Martin
    Biochemistry and Molecular Biology, Medical College of Georgia at Augusta University, Augusta, Georgia, United States
  • Footnotes
    Commercial Relationships   Folami Powell None; Shakera Thomas None; Pamela Martin None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1842. doi:
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    • Get Citation

      Folami Lamoke Powell, Shakera Thomas, Pamela M Martin; Novel GLP-1 secretagogues as neuroprotective agents for retinal neurodegenerative diseases. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1842.

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

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Abstract

Purpose : Glucagon-like peptide 1 (GLP-1) mimetics and receptor agonists are a class of anti-diabetic drugs that have been found to be neuroprotective in animal models, but the effects on retinopathy in humans remains controversial. GLP-1 secretagogues potentiate local release of GLP-1 stores in tissue and in turn exert local, insulinotropic functions, and may have different effects than the current class of GLP-1 drugs. Here, we examined the impact of GLP-1 secretagogues on the induction of GLP-1 secretion in the retina, retinal insulin synthesis, and morphological/functional in diabetes-induced retinal degeneration.

Methods : To investigate this normal, euglycemic mice were injected intraperitoneally with streptozotocin (STZ; 75 mg/kg in 0.01M sodium-citrate buffer, pH 4.5) to induce type 1 diabetes over a three-day period. GLP-1 secretagogues (JWU-A021 and BI-1046 (Boehringer Ingelheim)) and a negative control were delivered via single intravitreal injection or daily intraperitoneal dosing over a two-week period in non-diabetic and diabetic mice. The genes for insulin (INS1 and INS2) were quantified by qRT-PCR. Enzyme linked immunosorbent assay s(ELISA) were used to test for GLP-1, insulin, and C-peptide in the retinal tissues. Retinal sections were tested for the retinal stress-associated protein glial fibrillary acidic protein (GFAP). A terminal deoxynucleodtidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay was used to test the hypoglycemic mice retinas for apoptotic cells. Additionally, cryosections were stained with hematoxylin and eosin to examine the retinal morphological changes in treat and non-treated control and diabetic mice. Morphological and functional retinal changes were assessed using optical coherence tomography (OCT), scotopic electroretinogram (ERG) and optokinetic tracking analyses (OKT).

Results : Treatment with BI-1046 and JWU-A21 resulted in increased GLP-1 secretion and insulin gene expression and secretion. As reflected by significant improvements in retinal morphology, decreased stress factors, and function in STZ-diabetic mice, treatments with these GLP-1 secretagogues were largely beneficial.

Conclusions : We conclude that GLP-1 secretagogues are insulinotropic in the retina and can be promising therapeutic agents to combat retinal degeneration.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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