June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Investigating the role of p21CIP1/WAF1 in retinal vascular disease
Author Affiliations & Notes
  • Gabrielle Girouard
    Universite de Montreal, Montreal, Quebec, Canada
    Hopital Maisonneuve-Rosemont Centre de Recherche, Montreal, Quebec, Canada
  • Yusuke Ichiyama
    Hopital Maisonneuve-Rosemont Centre de Recherche, Montreal, Quebec, Canada
  • Roberto Diaz-Marin
    Universite de Montreal, Montreal, Quebec, Canada
    Hopital Maisonneuve-Rosemont Centre de Recherche, Montreal, Quebec, Canada
  • Guillaume Blot
    Hopital Maisonneuve-Rosemont Centre de Recherche, Montreal, Quebec, Canada
  • Rachel Juneau
    Hopital Maisonneuve-Rosemont Centre de Recherche, Montreal, Quebec, Canada
  • Frederique Pilon
    Hopital Maisonneuve-Rosemont Centre de Recherche, Montreal, Quebec, Canada
  • Vera Guber
    Hopital Maisonneuve-Rosemont Centre de Recherche, Montreal, Quebec, Canada
  • Agnieszka Dejda
    Hopital Maisonneuve-Rosemont Centre de Recherche, Montreal, Quebec, Canada
  • Sergio Crespo-Garcia
    Universite de Montreal, Montreal, Quebec, Canada
  • Przemyslaw Mike Sapieha
    Hopital Maisonneuve-Rosemont Centre de Recherche, Montreal, Quebec, Canada
  • Footnotes
    Commercial Relationships   Gabrielle Girouard None; Yusuke Ichiyama None; Roberto Diaz-Marin None; Guillaume Blot None; Rachel Juneau None; Frederique Pilon None; Vera Guber None; Agnieszka Dejda None; Sergio Crespo-Garcia None; Przemyslaw Mike Sapieha UNITY Biotechnology, Code E (Employment)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 5468. doi:
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      Gabrielle Girouard, Yusuke Ichiyama, Roberto Diaz-Marin, Guillaume Blot, Rachel Juneau, Frederique Pilon, Vera Guber, Agnieszka Dejda, Sergio Crespo-Garcia, Przemyslaw Mike Sapieha; Investigating the role of p21CIP1/WAF1 in retinal vascular disease. Invest. Ophthalmol. Vis. Sci. 2023;64(8):5468.

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

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Abstract

Purpose : Among vision-threatening pathologies, retinal vascular disease is the leading cause of blindness in industrialized countries. We previously identified that pathological neovascularization during oxygen-induced retinopathy (OIR) engage programs of cellular senescence. Cellular senescence is associated with the expression of genes involved in cell cycle arrest, such as p16INK4A and p21CIP1/WAF1. Although we demonstrated that ablation of p16 INK4A-expressing cells can halt pathological angiogenesis, the role of p21CIP1/WAF1 is yet to be studied.

Methods : Experimental pathological angiogenesis was achieved using oxygen-induced retinopathy (OIR; 75% O2 from P7 to P12) and laser-induced choroidal neovascularization (CNV) with mice deficient in p21CIP1/WAF1 (p21KO) and control C57Bl6/J (wildtype) mice. In OIR, the vasculature was analyzed at P14 and P17 with retina whole-mount preparations (immunohistochemistry) and the inflammatory profile of the retina was investigated by whole-retina qPCR. Laser-induced CNV was performed on 7–8-week-old males by rupturing the Bruch’s membrane using an argon laser. 14 days after CNV induction, mice were perfused with fluorescein isocyanate-dextran (FITC-dextran). Additionally, fixed choroids were labelled with Isolectin-B4 (IB4). 3 days after CNV induction, RPE-choroid-sclera complexes were collected for qPCR to investigate the inflammatory response.

Results : P21KO mice are less likely to survive the OIR-related oxygen challenge. However, surviving pups had reduced pathological neovascularization at P17 OIR. No changes were observed in vascular regeneration of ischemic retinas at P14 or P17 OIR. We observed a weaker induction of several inflammatory genes, including Vegfa, Serpine1, and Tnf, at P14 and P17 OIR in the p21KO mice. In the laser-induced CNV model, we found decreased CNV area (FITC-dextran) and a decreased burn area (IB4) in p21KO mice at D14. We also found a decrease of Il1b expression in P21KO mice RPE-choroid-sclera complexes at D3, though no changes were observed in Vegfa or Il6 expression between p21KO and controls.

Conclusions : Systemically, expression of p21CIP1/WAF1 may play a crucial role in controlling homeostasis regulation after hypoxic insult. In retinal and choroidal tissues, pathological neovascularization appears to be supported by p21CIP1/WAF1.

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

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