July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Longitudinal monitoring of Photoreceptor-RPE-Choroid Neurovascular Unit (PRC-NVU) morphology and function in the mouse model of Doyne Honeycomb Retinal Dystrophy
Author Affiliations & Notes
  • Robert J Zawadzki
    Ophthalmology & Vision Science, University of California Davis, Sacramento, California, United States
    Cell Biology and Human Anatomy, UC Davis, Davis, California, United States
  • Ratheesh Kumar Meleppat
    Cell Biology and Human Anatomy, UC Davis, Davis, California, United States
  • SUMAN MANNA
    Cell Biology and Human Anatomy, UC Davis, Davis, California, United States
  • Gabriel Peinado
    Cell Biology and Human Anatomy, UC Davis, Davis, California, United States
  • Sarah J Karlen
    Cell Biology and Human Anatomy, UC Davis, Davis, California, United States
  • Morgan Heisler
    Engineering Science, Simon Fraser University, Burnaby, British Columbia, Canada
  • Pengfei Zhang
    Cell Biology and Human Anatomy, UC Davis, Davis, California, United States
  • Marinko Sarunic
    Engineering Science, Simon Fraser University, Burnaby, British Columbia, Canada
  • Eric A Pierce
    Dept. of Ophthalmology, Harvard University, Boston, Massachusetts, United States
  • Edward N. Pugh
    Cell Biology and Human Anatomy, UC Davis, Davis, California, United States
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5822. doi:
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      Robert J Zawadzki, Ratheesh Kumar Meleppat, SUMAN MANNA, Gabriel Peinado, Sarah J Karlen, Morgan Heisler, Pengfei Zhang, Marinko Sarunic, Eric A Pierce, Edward N. Pugh; Longitudinal monitoring of Photoreceptor-RPE-Choroid Neurovascular Unit (PRC-NVU) morphology and function in the mouse model of Doyne Honeycomb Retinal Dystrophy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5822.

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

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Abstract

Purpose : To evaluate feasibility of in vivo retinal imaging methods for monitoring of Photoreceptor-RPE-Choroid Neurovascular Unit (PRC-NVU) morphology and function locally and longitudinally in individual animals during aging.

Methods : We repeatedly imaged Efemp1R345W/R345W mice of C57BL/6J background, and bred into the albino C57BL/6J-Tyr-c-Brd background and control albino C57BL/6J-Tyr-c-Brd and pigmented C57BL/6J mice to monitor longitudinal changes in (PRC-NVU) morphology and function. Efemp1R345W/R345W mice are a model of Doyne Honeycomb Retinal Dystrophy, an inherited macular degeneration, in which a point mutation in fibulin-3 causes basal deposits that effectively thicken BrM. Our in vivo measurements included (1) SLO-based autofluorescence mapping; (2) OCT-based: automated PRC-NVU complex morphology (layer thickness and changes in scattering); (3) bleaching-activated optophysiology; (4) automated OCTA-based choriocapillaris and choroidal vasculature mapping; (5) ERGs for analysis of rod-driven photoreceptor function.

Results : The lack of melanin in albino mice allowed investigation of BrM, Rods Outer Segments Tips (ROST) and choriocapillaris morphology, giving Efemp1R345W/R345W mice bred on an albino background a clear advantage for monitoring progression of retina degeneration in this model. The presence of melanin in pigmented mice makes direct measurements of BrM thickness impossible and mapping of choriocapillaris challenging. Both Efemp1R345W/R345W mouse strains showed accelerated deterioration of PRC-NVU complex structure and function as compared to age-matched controls.

Conclusions : In these studies, we use innovative, cellular-level resolution in vivo imaging combined with additional functional tests to characterize age-related changes in the structure and function of cells of the PRC-NVU in four cohorts of mice with the genetic defects, and in corresponding controls. Our ability to follow degeneration in vivo using imaging methods and automated image analysis allows a drastic reduction in the number of animals needed for these experiments, and permits fast analysis of correlative, local changes in structure and function.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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