June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Extracellular vesicles as nanocarrier of avastin to inhibit neovascularization for longer duration in diabetic retinopathy
Author Affiliations & Notes
  • Shivakumara Reddy
    Centre for Molecular Neurosciences, Kasturba Medical College Manipal, Manipal, Karnataka, India
  • Abhijna Ballal
    Centre for Molecular Neurosciences, Kasturba Medical College Manipal, Manipal, Karnataka, India
  • Shailaja S
    Opthalmology, Kasturba Hospital Manipal, Manipal, Karnataka, India
  • Raghu Chandrashekhar H
    Pharmaceutical Biotech, Manipal College of Pharmaceutical Sciences, Manipal, Karnataka, India
  • Shalini Adiga
    Pharmacology, Kasturba Medical College Manipal, Manipal, Karnataka, India
  • Dinesh Upadhya
    Centre for Molecular Neurosciences, Kasturba Medical College Manipal, Manipal, Karnataka, India
  • Footnotes
    Commercial Relationships   Shivakumara Reddy None; Abhijna Ballal None; Shailaja S None; Raghu Chandrashekhar H None; Shalini Adiga None; Dinesh Upadhya None
  • Footnotes
    Support  NONE
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 2197 – F0260. doi:
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      Shivakumara Reddy, Abhijna Ballal, Shailaja S, Raghu Chandrashekhar H, Shalini Adiga, Dinesh Upadhya; Extracellular vesicles as nanocarrier of avastin to inhibit neovascularization for longer duration in diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2197 – F0260.

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

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Abstract

Purpose : Diabetic Retinopathy (DR) is a common complication of diabetes mellitus demonstrating neovascularization and remains a leading cause of loss of vision. Treatment of DR focuses on targeting vascular endothelial growth factor (VEGF) to reduce neovascularization with repeated intravitreal injections. The complications with repeated intravitreal injections are retinal detachment, trauma, etc. To reduce the frequency of intravitreal injections, we loaded ant-VEGF drug into small extracellular vesicles (sEVs) as recent reports suggested the ability of EVs in sustained drug delivery. The ability of the anti-VEGF loaded sEVs were tested for their sustained antiangiogenic potential in STZ induced rat model of DR.

Methods : Small EVs were isolated from bone marrow-derived mesenchymal stromal cells (BM-MSC) and characterized. Avastin was loaded into sEVs by freeze-thaw, co-incubation 0.2% saponin, and sonication methods. Avastin loaded in EVs was checked for its antiangiogenic properties by chorioallantoic Membrane (CAM) assay in the egg chick embryo. To tract the avastin loaded EVs in the retina, FITC conjugated avastin was loaded into PKH26 labeled sEVs. Further, DR was induced in Wistar Albino rats through administration of streptozotocin. Blood sugar levels were monitored multiple times over months after the STZ injection, and the presence of exudates in the retina was confirmed by FITC-dextran perfusion. The effect of anti-VEGF-loaded EVs on neovascularization was evaluated at different time intervals using VEGF immunostaining.

Results : Characterization of EVs using NanoSight tracking demonstrated a mean size of 167nm, and TEM analysis revealed cup-shaped morphology, and western blot analysis revealed positive for TSG101 and CD 63 while negative for GM130. Significant amounts of avastin was loaded by all the tested methods. The avastin loaded EVs significantly inhibited the angiogenesis in the CAM assay. We have tracked avastin-loaded EVs in different retina layers in naive rats. In DR, avastin loaded EVs decreased the number of exudates in the retina, and the VEGF expression was low in the avastin loaded EV group compared to avastin alone group over a period of time.

Conclusions : Due to sustained drug delivery ability, avastin loaded EVs may be ideal for the controlled release of avastin for a longer duration to inhibit neovascularization in DR.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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