June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
PEDF protects photoreceptors via a CRX-dependent mechanism
Author Affiliations & Notes
  • Ivan Rebustini
    Section on Protein Structure and Function, National Eye Institute, Bethesda, Maryland, United States
  • S Patricia Becerra
    Section on Protein Structure and Function, National Eye Institute, Bethesda, Maryland, United States
  • Footnotes
    Commercial Relationships   Ivan Rebustini, None; S Patricia Becerra, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2966. doi:
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      Ivan Rebustini, S Patricia Becerra; PEDF protects photoreceptors via a CRX-dependent mechanism. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2966.

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

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Abstract

Purpose : Pigmented Epithelium-Derived Factor (PEDF) is a neuroprotective peptide expressed and secreted by the Retinal Pigmented Epithelium (RPE) and protects photoreceptors from apoptosis during genetic- related retinal degeneration such as Retinitis Pigmentosa (RP). PEDF-derived peptides protect photoreceptors from apoptosis in rd10 mice, a RP model with mutated Phosphodiesterase 6b (PDE6b). Many forms of RP are also associated with dysregulation of Cone and Rod Homeobox (CRX), which is a transcription factor necessary for photoreceptors differentiation and regulates the transcription of more than 700 genes associated with photoreceptors function, among them the Phosphodiesterase 6a (PDE6a), which is involved in the visual phototransduction system in the photoreceptors. Although rod photoreceptors express both PDE6a and PD6b phosphodiesterase subunits, it is unclear whether there is a compensatory mechanism involving PEDF signaling and CRX expression in mouse models of RP. The purpose of this study is to address whether the mechanisms of PEDF-induced photoreceptor protection involves CRX expression and its regulatory gene network.

Methods : We employed a wild-type mouse retinal explant model and Zaprinast, a broad-range phosphodiesterase inhibitor to establish a model of general induction of photoreceptor cell death and define the molecular mechanisms of PEDF as neuroprotective to photoreceptors. We used whole mount immunofluorescence after treating the mouse retinal explants with combinations of PEDF and Zaprinast, to characterize cellular processes such as apoptosis via TUNEL and the expression of CRX and various photoreceptor markers by confocal microscopy super resolution imaging.

Results : We established a quantitative imaging methodology to assess photoreceptors maintenance and survival in mouse retinal explants by using super resolution confocal microscopy, and found that PEDF treatment increased CRX expression in surviving photoreceptors in Zaprinast-treated retinal explants and decreased apoptosis, suggesting that PEDF signaling regulates photoreceptors survival via a CRX-dependent mechanism.

Conclusions : We postulate that CRX expression is downstream to PEDF signaling and is a regulatory key component for photoreceptor survival upon retinal degeneration disease induction.

This is a 2021 ARVO Annual Meeting abstract.

 

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