July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Elucidating the role of photoreceptors in AMD pathogenesis
Author Affiliations & Notes
  • Shun-Yun Cheng
    Ophthalmology, University of Massachusetts Medical School, Worcester, Massachusetts, United States
  • Joris Cipi
    Ophthalmology, University of Massachusetts Medical School, Worcester, Massachusetts, United States
  • Martin-Paul Agbaga
    phthalmology, Cell Biology & OCNS, Univ. of Oklahoma Health Sciences Center, Oklahoma, United States
  • Shan Ma
    New England College of Optometry, Massachusetts, United States
  • Claudio Punzo
    Ophthalmology, University of Massachusetts Medical School, Worcester, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Shun-Yun Cheng, None; Joris Cipi, None; Martin-Paul Agbaga, None; Shan Ma, None; Claudio Punzo, None
  • Footnotes
    Support  Bright Focus Fundation M2017071
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1220. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Shun-Yun Cheng, Joris Cipi, Martin-Paul Agbaga, Shan Ma, Claudio Punzo; Elucidating the role of photoreceptors in AMD pathogenesis. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1220.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Retinal pigmented epithelium (RPE) cells are the primary cell type affected in age-related macular degeneration (AMD); however, the extrinsic factors contributing to RPE dysfunction remain unclear. Data from macular translocation procedures and from Stargardt’s patients suggest that photoreceptors may partake in RPE pathogenesis. To elucidate the role of photoreceptors in AMD pathogenesis we looked at differences in photoreceptor metabolism between AMD patients and non-diseased individuals and recapitulated those changes in mouse.

Methods : To mimic the metabolic pattern seen in photoreceptors of AMD patients we genetically manipulate the mammalian target of rapamycin (mTOR) pathway specifically in photoreceptors of mice by use of the Cre-lox system. Mice where followed over time by funduscopy and histological analyses.

Results : We found that photoreceptors in AMD patients express higher levels of a key aerobic glycolysis gene when compared to photoreceptors of non-diseased individuals. Mimicking this change in mouse photoreceptors resulted in pathologies consistent with pathologies seen in AMD patients. These include sub-RPE and sub-retinal drusen-like deposits, Bruch’s membrane thickening and lipid deposition within the Bruch’s membrane, RPE dysfunction and atrophy including geographic atrophy (in 20% mice) and neovascular pathologies (in 8% of mice). Finally, combining the changes in rods and cones accelerated disease progression.

Conclusions : The data suggests that photoreceptors contribute to AMD pathogenesis, explaining why AMD affects primarily the macular region, as this is the area with the highest photoreceptor density. This finding opens new avenues for therapeutic intervention to treat AMD at earlier stages.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×