Joe Hollyfield, PhD, receives 2009 Proctor Medal, describes mouse model of AMD

Fort Lauderdale, FL-Joe Hollyfield, PhD, received the distinguished Proctor Medal, the highest honor bestowed by the Association for Research in Vision and Ophthalmology. Dr. Hollyfield, director of ophthalmic research, Cole Eye Institute, Cleveland Clinic, Cleveland, delivered the Proctor Lecture titled “Progress in Understanding the Initiating Events in Age-Related Macular Degeneration [AMD].” While at the Cleveland Clinic, his laboratory identified the composition of drusen, the major risk factor for AMD.

Dr. Hollyfield described the steps in the development of a mouse model of AMD-work that is ongoing. With the recognition that carboxyethylpyrrole (CEP) adducts are more abundant in AMD and are present in drusen and Bruch’s membrane, he theorized that CEP, which arises from oxidation of docosahexaenoate (DHA)-containing lipids, might be the signature oxidation product that is the initiating event in AMD.

“If CEP is the initiating epitope in AMD, then mice immunized with CEP will be sensitized to CEP and develop an AMD-like pathology in the outer retina as CEP adducts are formed during the lifetime of the mice,” Dr. Hollyfield said.

This theory resulted in a mouse model in which, according to Dr. Hollyfield, C57BL/65 mice were immunized with an inflammatory fragment of DHA that is present in AMD donor eyes. The mice produce antibodies deposited as complement 3 in Bruch’s membrane, subretinal pigment epithelial laminar deposits develop, form localized electroretinogram and photoreceptor pathologies, and finally develop decreased retinal function (loss of rods and cones) in the form of decreased a- and b-wave amplitudes.

Dr. Hollyfield and colleagues are in the process of developing various knockout lines of mice that will be used to investigate difference aspects of the activation pathways.