AMD-like lesions in the rat retina: a latent consequence of perinatal hemorrhage

Abstract

Purpose: Hemorrhaging is a commonplace event in the human retina around the time of birth. This study was conducted to examine the potential long-term sequelae of hemorrhaging in the eyes of rats that exhibited transient spontaneous microhemorrhages a few days after birth.

Methods: Retinas of Dark Agouti rats aged from day of birth to 2 years old were analyzed histologically, histochemically, and by immunocytochemistry. Fetal human retinas were also examined anatomically and histochemically for evidence of hemorrhages.

Results: Dark Agouti rats from our colony consistently exhibited spontaneous focal hemorrhages at the vitread surface of the retina between postnatal days 3 and 6. Erythrocytes were subsequently cleared by macrophages, which accumulated hemosiderin. These macrophages remained in focal patches in the inner retina for the duration of the study. For at least 6 months after the initial transient hemorrhages, the retinas exhibited no overt histologic damage. At approximately 8 to 9 months, photoreceptor degenerative changes were apparent in spatial register with the patches of macrophages in the inner retina. Additional events such as breakdown of Bruch's membrane, glial remodeling, neovascularization, ingress of RPE cells into the retina and accumulation of drusen-like autofluorescent structures were also observed in topographic register with macrophage-laden patches in aged animals.

Conclusions: Microhemorrhages in the retina may initiate the formation of focal lesions, months or years after the initial insult. The lesions exhibit key features of AMD. These animals may represent a useful model for studying the potential basis of the pathogenesis of AMD.