Reticular Fundus Autofluorescence (FAF) In The Evolution Of Geographic Atrophy (GA) In A Rat Model Of RPE Toxicity

Abstract

 

Purpose:

 

using in vivo investigations, to describe a rodent model of non-exudative AMD that evolves from a complex clinically-relevant pattern of FAF to geographic atrophy, thus mimicking this advanced and blinding step in disease progression and providing a powerful model for pre-clinical evaluation.

 

Methods:

 

the systemic RPE toxin, sodium iodate (NaIO3 45mg/kg) was injected via tail vein in Sprague Dawley rats. Using confocal scanning laser ophthalmoscopy, FAF (488/520nm), infra-red (820nm), and red-free images were obtained, along with optical coherence tomography (OCT) and flash ERG data, at intervals out to 4.5 months. Excised retina and posterior eye cups were histologically evaluated by H&E.

 

Results:

 

in vivo imaging reveals three distinct phases of progression - (i) fluid flux across the RPE-retinal barrier, (ii) formation of a reticular pattern of alternating hyper/hypo FAF that corresponds with changes in RF and IR channels, accompanied by development of discrete and inter-connected hyperfluorescent subretinal deposits, halos, and target lesions and finally, (iii) reduction or burn-out of this pattern leaving frank tissue loss. On histological exam, these in vivo observations correspond with (i) breakdown of blood retinal barrier, (ii) progressive deformation of the outer retina with accumulation of subretinal inflammatory cells / debris, and (iii) thinning and atrophy

 

Conclusions:

 

to our knowledge, this is the first description of a rodent model of non-exudative AMD that develops a complex pattern of FAF. Significantly, this pattern bears striking resemblance to the junctional zones of advancing non-exudative AMD and to reticular pseudodrusen, both of which correlate with rapid clinical decline. This model also recapitulates the important clinically-observed transition from hyperfluorescent signal to geographic tissue loss. Studies of therapeutic intervention are underway.

 

Keywords: age-related macular degeneration • retinal pigment epithelium • imaging/image analysis: non-clinical