June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Efficacy and impact of the melanocortin receptor agonists PL8177 and PL9654 in an STZ-rat model of diabetic retinopathy (DR)
Author Affiliations & Notes
  • Paul Kayne
    Palatin Technologies. Inc., Cranbury, New Jersey, United States
  • Priyanka Dhingra
    Palatin Technologies. Inc., Cranbury, New Jersey, United States
  • Alison Obr
    Palatin Technologies. Inc., Cranbury, New Jersey, United States
  • John Dodd
    Palatin Technologies. Inc., Cranbury, New Jersey, United States
  • Carl Spana
    Palatin Technologies. Inc., Cranbury, New Jersey, United States
  • Footnotes
    Commercial Relationships   Paul Kayne Palatin Technologies, Inc, Code E (Employment); Priyanka Dhingra Palatin Technologies, Inc., Code E (Employment); Alison Obr Palatin Technologies, Inc., Code F (Financial Support); John Dodd Palatin Technologies, Inc., Code E (Employment); Carl Spana Palatin Technologies, Inc., Code E (Employment)
  • Footnotes
    Support  Palatin Technologies. Inc.
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 3592 – A0047. doi:
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    • Get Citation

      Paul Kayne, Priyanka Dhingra, Alison Obr, John Dodd, Carl Spana; Efficacy and impact of the melanocortin receptor agonists PL8177 and PL9654 in an STZ-rat model of diabetic retinopathy (DR). Invest. Ophthalmol. Vis. Sci. 2022;63(7):3592 – A0047.

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

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Abstract

Purpose : Anti-inflammatory benefits of the melanocortin system suggest that melanocortin receptor (MCr) agonists have promise in the treatment of inflammatory diseases. The selective MC1r agonist, PL8177 and the MC1r/MC3r/MC4r/MC5r pan-agonist PL9654, were investigated in a streptozotocin (STZ) rat model of DR and their effects on ocular inflammation, retinal cell population composition, and gene and protein expression were determined. The objective was to determine the effectiveness of PL8177 and PL9654 in this model and to characterize its mechanism of action.

Methods : Effect of PL8177 and PL9654 on vision was investigated in a 114-day study. STZ-rats were randomly assigned to 5 separate study arms. On days 4–113, rats received BID subcutaneous administration of vehicle (0.9% NaCl); PL9654 0.05mg/kg, 0.1mg/kg, or 0.5mg/kg; or PL8177 1mg/kg. Visual function was measured by optokinetic tracking every 2 wks from day 43 to day 113. Cataract images were acquired after each optokinetic session. Rats were euthanized on day 114. Right-eye retinas were dissected and snap-frozen; left eyes were enucleated and fixed for histology. Retinal thickness and photoreceptor degeneration/loss were measured.

Results : PL9654 doses of 0.05–0.5mg/kg and PL8177 at 1mg/kg showed significant efficacy in reducing vision loss in STZ-treated rats compared to vehicle. PL9654 0.1 and 0.5mg/kg significantly reduced loss of both visual acuity and contrast vision. At 0.05mg/kg, PL9654 significantly reduced loss of contrast vision. PL8177 1mg/kg significantly reduced loss of visual acuity. Histopathology showed that there was significantly less photoreceptor degeneration with PL9654 0.1mg/kg vs vehicle(P<0.05). Retinal thickness was also significantly improved for the PL9654(P<0.05) and PL8177(P<0.05) groups vs vehicle. There were no adverse events resulting from administration of either PL9654 or PL8177. Changes in the cellular population compositions, gene expression changes and protein level data will be presented and discussed at the conference.

Conclusions : SC BID administration of the melanocortin agonists PL9654 and PL8177 show promise in the treatment of DR by reducing vision loss and photoreceptor degeneration in the STZ-rat model of DR. Single nuclei RNAseq and proteomic data will be interpreted in the context of disease change to identify alterations in immune and cellular states of the rat retinas.

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

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