June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Loss of melanopsin results in late-onset cone photoreceptor degeneration
Author Affiliations & Notes
  • Sujata Rao
    Ophthalmic Research, Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Kenya Wilcots
    Ophthalmic Research, Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
    Chemistry, Cleveland State University, Cleveland, Ohio, United States
  • Rebecca Fuller
    Ophthalmic Research, Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • rupesh singh
    Ophthalmic Research, Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Ivy samuels
    Louis Stokes VA Medical Center, Cleveland, Ohio, United States
    Ophthalmic Research, Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Minzhong Yu
    Ophthalmic Research, Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • John W Crabb
    Ophthalmic Research, Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, United States
  • Footnotes
    Commercial Relationships   Sujata Rao None; Kenya Wilcots None; Rebecca Fuller None; rupesh singh None; Ivy samuels None; Minzhong Yu None; John Crabb None
  • Footnotes
    Support  NIH-NEI P30 Core Grant (IP30EY025585), Unrestricted Grants from The Research to Prevent Blindness, Inc., and Cleveland Eye Bank Foundation awarded to the Cole Eye Institute.
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 978 – F0375. doi:
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    • Get Citation

      Sujata Rao, Kenya Wilcots, Rebecca Fuller, rupesh singh, Ivy samuels, Minzhong Yu, John W Crabb; Loss of melanopsin results in late-onset cone photoreceptor degeneration. Invest. Ophthalmol. Vis. Sci. 2022;63(7):978 – F0375.

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

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Abstract

Purpose : Melanopsin (Opsin 4) is a photopigment expressed in the retinal ganglion cells and is critical for non-image forming vision. The goal of this study was to determine the role of melanopsin signaling for maintaining retinal integrity and function.

Methods : Opn4-/- and wild-type littermate control animals were longitudinally assessed from 3 months (M) to 14M using optical coherence tomography (OCT) based measurements. OCT findings were validated using immunofluorescence and protein blots. Transcriptomic (RNA Seq) and proteomic analyses of the retina were carried out at 4M and 12M. Rates of degradation of phagosomes and the diurnal exposure of phosphatidylserine was measured using anti-rhodopsin and Annexin A5.

Results : Loss of melanopsin results in late-onset degeneration of the retina with spatiotemporal differences in the progression of the photoreceptor degeneration. For example, medium opsin (M-opsin) is reduced at 12M in Opn4-/- retinas, with a severe reduction in the dorsal region of the retina. A similar dorsal-ventral gradient in outer nuclear layer thickness was detected. Electroretinography (ERG) analysis failed to detect any changes in the rod photoreceptor responses but cone responses were significantly reduced. A morphometric analysis of the RPE indicates changes in RPE cell size accompanied by an overall reduction in cell junction proteins in the Opn4-/- mutants. Our preliminary assessments suggest that the RPE changes preclude retinal degeneration. Accordingly, the degradation of phagosomes appears to be delayed suggesting that the rhythm of RPE phagocytosis is altered in the Opn4-/- animals. The diurnal exposure of phosphatidylserine is persistent suggesting that the early stages of phagocytosis are affected. The retinal and RPE pathologies are age-related and do not manifest in animals younger than eight months old.

Conclusions : Melanopsin signaling plays an important role during retinal development, however, the contribution of this signaling axis in retinal homeostasis is not well understood. Here we provide evidence that melanopsin signaling plays a critical role in protecting the aging retina from damage. Moreover, our data suggest that melanopsin signaling may play a critical role in the phagocytosis of the photoreceptor outer segment and raises the possibility that melanopsin could function in the RPE.

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

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