Death by color: differential cone loss in the aging mouse retina

Differential cell death is a common feature of aging and age-related disease. In the retina, 30% of rod photoreceptors are lost over life in humans and rodents. However, studies have failed to show age-related cell death in mouse cone photoreceptors, which is surprising because cone physiological function declines with age. Moreover in human, differential loss of short wavelength cone function is an aspect of age-related retinal disease. Here, cones are examined in young (3-month-old) and aged (12-month-old) C57 mice and also in complement factor H knock out mice (CFH-/-) that have been proposed as a murine model of age-related macular degeneration. In vivo imaging showed significant age-related reductions in outer retinal thickness in both groups over this period. Immunostaining for opsins revealed a specific significant decline of >20% for the medium/long (M/L)-wavelength cones but only in the periphery. S cones numbers were not significantly affected by age. This differential cell loss was backed up with quantitative real-time polymerase chain reaction for the 2 opsins, again showing S opsin was unaffected, but that M/L opsin was reduced particularly in CFH-/- mice. These results demonstrate aged cone loss, but surprisingly, in both genotypes, it is only significant in the peripheral ventral retina and focused on the M/L population and not S cones. We speculate that there may be fundamental differences in differential cone loss between human and mouse that may question the validity of mouse models of human outer retinal aging and pathology

Multidisciplinary Ophthalmic Imaging In Vivo Imaging of a New Indocyanine Green Micelle Formulation in an Animal Model of Laser-Induced Choroidal Neovascularization

METHODS. The ICG was formulated with the nonionic solubilizer and emulsifying agent Kolliphor HS 15 to create ICG/HS 15 to improve the chemical stability and fluorescence efficacy. In vivo imaging was performed in rats that had undergone laser photocoagulation. Retinal uptake and fluorescence intensity of ICG and ICG/HS 15 were compared following intravenous injection of 3 dosages (0.05, 0.1, and 0.15 mg/kg body weight) at 7, 14, and 21 days following laser treatment. Postmortem analysis included histology with frozen sections and flat mounts. RESULTS. Immediately following injection of ICG or ICG/HS 15, a strong fluorescence was visible in the retinal vasculature and at the site of laser lesions. Pixel intensity was higher for ICG/HS 15 compared to conventional ICG at 8 minutes after injection for all different injection days and dosages. Over time, a continuous decrease of the fluorescent signal was observed for up to 60 minutes to baseline level. Flow cytometry data showed an increased uptake of micellar dye of macrophages and endothelial cells. Histology revealed an accumulation of the micellar dye within the laser lesion. CONCLUSIONS. Micelle formulated ICG can be visualized in the retinal vasculature and laserinduced CNV in vivo and ex vivo. Micellar ICG/HS 15 showed in vivo stronger signal intensity when compared to ICG for all tested dosages. Following further investigations, ICG/HS 15 may be evaluated in patients with retinal and choroidal diseases for more refined diagnosis