June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Cyto-protective effect of neuropeptide alpha-Melanocyte-Stimulating Hormone on UV-A irradiation-induced Fuchs Endothelial Corneal Dystrophy
Author Affiliations & Notes
  • Francesca Kahale
    Ophthalmology, Massachusetts Eye and Ear Department of Ophthalmology, Boston, Massachusetts, United States
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Neha Deshpande
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Hamid Alemi
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Shudan Wang
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Tomas Blanco
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
    Harvard University, Boston, Massachusetts, United States
  • Thomas H Dohlman
    Ophthalmology, Massachusetts Eye and Ear Department of Ophthalmology, Boston, Massachusetts, United States
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Jia Yin
    Ophthalmology, Massachusetts Eye and Ear Department of Ophthalmology, Boston, Massachusetts, United States
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Ula V Jurkunas
    Ophthalmology, Massachusetts Eye and Ear Department of Ophthalmology, Boston, Massachusetts, United States
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Reza Dana
    Ophthalmology, Massachusetts Eye and Ear Department of Ophthalmology, Boston, Massachusetts, United States
    Schepens Eye Research Institute of Massachusetts Eye and Ear, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Francesca Kahale None; Neha Deshpande None; Hamid Alemi None; Shudan Wang None; Tomas Blanco None; Thomas Dohlman None; Jia Yin Kera therapeutics , Code O (Owner); Ula Jurkunas None; Reza Dana Kera therapeutics , Code O (Owner)
  • Footnotes
    Support  R21EY032695
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 2751 – A0240. doi:
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    • Get Citation

      Francesca Kahale, Neha Deshpande, Hamid Alemi, Shudan Wang, Tomas Blanco, Thomas H Dohlman, Jia Yin, Ula V Jurkunas, Reza Dana; Cyto-protective effect of neuropeptide alpha-Melanocyte-Stimulating Hormone on UV-A irradiation-induced Fuchs Endothelial Corneal Dystrophy. Invest. Ophthalmol. Vis. Sci. 2022;63(7):2751 – A0240.

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

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Abstract

Purpose : Fuchs Endothelial Corneal Dystrophy (FECD) is characterized by a progressive loss of corneal endothelial cells (CEnC) from accumulated exposure to oxidative stress. It is one of the leading causes of corneal transplantation worldwide, and no definitive pharmacologic treatment is available. We have previously demonstrated the cytoprotective function of the neuropeptide alpha-Melanocyte-Stimulating Hormone (α-MSH) against oxidative stress in CEnC ex vivo. This study aims to investigate the in vivo protective effect of α-MSH in a mouse model of FECD induced by UV-A irradiation.

Methods : 8-week-old female BALB/c mice (n=6/group) were irradiated with UV-A at 500J/cm2 for 16 minutes. Mice received an intraperitoneal injection of 0.01mL/g of α-MSH (10-4 M) immediately following irradiation and thrice weekly for 8 weeks. The control group received no treatment. CEnC density, hexagonality, and cell size variability (CV) were evaluated by in vivo confocal microscopy pre-irradiation and at 1, 2, and 4 weeks post-irradiation. ZO-1 staining was performed at 8 weeks. Corneal edema was evaluated by measuring central corneal thickness on OCT.

Results : At 4 weeks post-irradiation in the control treatment group, there was a 50.5% decrease in CEnC density (1373±199 cell/mm2 vs baseline 2773±66, p=0.002), a 29% decrease in hexagonality (41±2.5 vs baseline 57.8±1.7, P=0.032) and a 61% increase in polymegathism (CV: 58±1.22 vs baseline 36±1.3, P=0.001). Compared to controls, the α-MSH treatment group demonstrated significant improvements in these parameters: the decrease in CEnC density was 18.7% (2255±116 vs control 1373±199, P=0.012), the decrease in hexagonality was 6.7% (53.9±2 vs control 41±2.5, P=0.014) and the increase in polymegathism was 8.6% (39±1.8 vs control 58±1.22, P=0.007). Corneal thickness was assessed in N=4 mice at 4 weeks where edema subsided in the α-MSH treatment group but remained elevated in the control group (107.8 ±14.6µm vs 166.3±39.4µm, p<0.05).

Conclusions : Intraperitoneal treatment with α-MSH leads to decreases in UV-A-induced CEnC cell loss, polymegathism and pleomorphism, along with resolution of corneal edema.

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

 

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