June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Inhibition of ischemia/reperfusion-induced retinal capillary degeneration in mice by peptain-1
Author Affiliations & Notes
  • Rooban B Nahomi
    Ophthalmology, University of Colorado, Denver, Colorado, United States
  • Mi-Hyun Nam
    Ophthalmology, University of Colorado, Denver, Colorado, United States
  • Clarinda Hougen
    Ophthalmology, University of Colorado, Denver, Colorado, United States
  • Noelle Carrillo
    Ophthalmology, University of Colorado, Denver, Colorado, United States
  • Ram H Nagaraj
    Ophthalmology, University of Colorado, Denver, Colorado, United States
  • Footnotes
    Commercial Relationships   Rooban Nahomi, None; Mi-Hyun Nam, None; Clarinda Hougen, None; Noelle Carrillo, None; Ram Nagaraj, None
  • Footnotes
    Support  National Institutes of Health Grants EY028836 and EY023286 , Research to Prevent Blindness to the Department of Ophthalmology, University of Colorado.
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 1165. doi:
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    • Get Citation

      Rooban B Nahomi, Mi-Hyun Nam, Clarinda Hougen, Noelle Carrillo, Ram H Nagaraj; Inhibition of ischemia/reperfusion-induced retinal capillary degeneration in mice by peptain-1. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1165.

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

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Abstract

Purpose : Retinal capillary endothelial cells undergo apoptosis in diabetic retinopathy (DR). Peptain-1 is a cell-permeable αB-crystallin-derived peptide and it exhibits strong antiapoptotic properties. Here, we investigated the ability of peptain-1 to inhibit apoptosis in cultured retinal endothelial cells and in retinal capillaries of mice subjected to retinal ischemia/reperfusion (I/R) injury.

Methods : Human retinal endothelial cells (HRECs) were treated with peptain-1 or scrambled peptides (200 μg/ml) for 3 h, and a combination of pro-inflammatory cytokines [IFN-γ (50 U/ml) + TNF-α (20 ng/ml) + IL-1β (20 ng/ml)] for 48 h. Twelve-week-old C57BL/6J mice were subjected to I/R injury by elevating the intraocular pressure to 120 mmHg for 60 min followed by reperfusion. Peptain-1 or scrambled peptide (500ng/μl of PBS) was injected intravitreally immediately after and one week after I/R injury. The PBS injected eyes were used as vehicle controls and the animals were euthanized on day 14 post-I/R injury. Abnormalities in the retinal capillaries were evaluated by staining the elastase-digested retinal blood vessels using Periodic acid–Schiff stain.

Results : Our results suggest that peptain-1 entered HRECs and blocked the pro-inflammatory cytokine-mediated apoptosis. Intravitreally injected peptain-1 was distributed throughout the retina after 4 h. The I/R injury caused a significant increase in acellular capillaries in the retina (3.5-fold when compared to controls), while intravitreally injected peptain-1, but not scrambled peptide, protected those cells from I/R injury (1.5-fold increase when compared to the control group).

Conclusions : Our study demonstrated that peptain-1 protects retinal capillary cells from I/R injury and suggests that it could be used as a therapeutic agent to prevent capillary cell death in DR.

This is a 2021 ARVO Annual Meeting abstract.

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