Abstract
Purpose :
Age-related macular degeneration (AMD) is one of the leading causes of blindness and currently no therapy is available for the dry form of AMD (dAMD). Lack of translatable animal model of dAMD posts significant obstacle for the discovery and development of therapeutics for the disease. To address this, we screened a colony of aged cynomolgus monkeys for drusen, a hallmark of AMD. The animals were further characterized by optical coherence tomography (OCT) to evaluate their utility as an animal model of dAMD.
Methods :
Four-hundred twenty-three cynomolgus monkeys from a breeding colony, age 10 to 25 years with an average age of 15.6 years, were examined for the presence of drusen-like changes by color fundus photography and further characterized by OCT (Spectralis OCT-Plus, Heidelberg, Germany). The size and characteristics of the drusen were compared to that of the human and a 6-month follow-up was carried out to track the changes of the drusen.
Results :
From the screening, 32 animals (7.6%), average age 15.9 years, were identified with drusen. The number of drusen presence in drusen positive eyes ranges from a few to over one thousand. Similar to human, most of the drusen deposited between Bruch’s membrane and retinal pigment epithelium (RPE) and size ranges from small (<63 um), intermediate (63-125 um) to large (>125 um). Reticular drusen are also observed. Estimated individual drusen volume ranges from 0.06 x 106 um3 to 4.88 x 106 um3. Impacts of the drusen on retina thickness, RPE and other retina layers were noticed. Follow-up examination of drusen positive eyes revealed changes in drusen size with an estimated 14% average increase in volume over a course of 6 months.
Conclusions :
A group of animals with spontaneous drusen has been identified in a colony of aged cynomolgus monkeys. OCT examination revealed that these drusen have many characteristics of the human drusen and are corresponding to early and intermediate stage of AMD. Given the critical role of drusen in the development of AMD and the ability of using OCT to quantify and track the change of the drusen provides a novel means to using these animals as a dAMD animal model.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.