July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
A Zebrafish Model for AMD Pathogenesis and Treatment
Author Affiliations & Notes
  • D Joshua Cameron
    Optometry, Western Univ of Hlth Sciences, Upland, California, United States
  • Footnotes
    Commercial Relationships   D Joshua Cameron, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1230. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      D Joshua Cameron; A Zebrafish Model for AMD Pathogenesis and Treatment. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1230.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Age-related macular degeneration (AMD) is defined as an abnormality of the retinal pigment epithelium (RPE) that leads to overlying photoreceptor degeneration of the macula and consequent loss of central vision. In dry AMD numerous large drusen form in Bruch’s membrane, which runs from the innermost layer of the choroid to the RPE; these extracellular deposits consist of lipids, zinc, apoplipoprotein and amyloid-beta(Aβ). Additionally, lipofuscin and A2E have been suggested to be involved in macular degeneration pathogenesis. The accessibility of its eye and the success of recent treatments in our lab suggest that zebrafish would make an ideal model to study the effects these AMD associated compounds and possible treatment strategies.

Methods : Adult zebrafish undergo an ocular assessment including a measurement of IOP, retina, and visual acuity as established previously. The AMD associated molecules, A2E and Aβ, are injected into normal, healthy adult zebrafish eyes. Protective zeaxanthin is also injected in some animal eyes. Control eyes receiving injections of saline are also used. Follow-up exams are completed to assess the IOP, retina, and visual acuity.

Results : The IOP in the fish did not appear to significantly change after injections for a period of up 8 weeks after injection. Injections of 50µM A2E resulted in a visual acuity deficit. Higher doses of 100µM also showed a reduction in visual acuity. No noticeable changes were observed in the retina. Unexpectedly, 2.25µM Aβ significantly increased visual acuity compared to PBS injected controls. The Aβ treated eyes also developed new capillary growth near the circumferential vein. Injections with zeaxanthin led to elevated visual acuity, even in the A2E and Aβ treated eyes, though the effects were more pronounced in the A2E treated eyes. Zeaxanthin did not affect the formation of new capillaries in the Aβ treated eyes. Visual acuity changes in all of the fish is not permanent. Most returned to the same visual function within 8 weeks after injection.

Conclusions : Injection of the AMD associated compounds, A2E and Aβ, affects visual function in the adult zebrafish. Functional and structural changes are noted and suggest that the adult zebrafish may be useful for studying factors related to the etiology of AMD. Zeaxanthin and other carotenoids may be useful in protecting the retina from AMD associated factors. Recovery after intraocular injections complicates longitudinal studies.

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.

×