Brief Exposure to Damaging Light Causes Focal Recruitment of Macrophages, and Long-Term Destabilization of Photoreceptors in the Albino Rat Retina

Abstract

Purpose: To characterize the long-term spatiotemporal features of light-mediated retinal degeneration.

Methods: Sprague–Dawley rats were exposed to 1000 lux for 24 h, then kept in dim light (5 lux), for up to 56 days. Animals were killed at 0, 3, 7, 28, and 56 days post-exposure, and retinas were prepared for immunohistochemistry. Outer nuclear layer (ONL) thickness and TUNEL labeling were used to quantify photoreceptor death. Antibodies to opsins, glial fibrillary acidic protein (GFAP), fibroblast growth factor-2 (FGF-2), and ED1 were used to assess the retina.

Results: At 0 days post-exposure, we detected photoreceptor death 2 mm superior to the optic disc (the “hotspot”), and ED1-positive macrophages in the retinal vasculature and underlying choroid. By 3 days, the ONL was thinner and there was gliosis in the outer retina, where ED1 positive macrophages were also present. Few ED1 positive cells remained at 28 days. At 56 days, there were TUNEL-positive nuclei in the penumbra, and increased FGF-2, and GFAP expression by Müller cells (MCs). In inferior retina, outer segment length was initially reduced, but recovered to near-normal by 28 days.

Conclusions: Short exposure to damaging light destabilizes the retina adjacent to a hotspot of degeneration, so that the damaged region expands in size over time. Recruitment of macrophages is associated with the early phase of damage, but not with the longer term photoreceptor loss in the penumbra. Features of the focal and progressive retinal damage in this model are reminiscent of the progression of age-related macular degeneration (AMD).

KEYWORDS::

• Age-related macular degeneration
• Blood–retinal barrier
• Light damage
• Macrophages
• Photoreceptor dystrophy
• Retina

ACKNOWLEDGMENT

This work was supported by Australian Research Council Centres of Excellence Program (CE0561903); Ophthalmic Research Institute of Australia/Brenda Mitchell grant.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.