Retbindin mediates light-damage in mouse retina while its absence leads to premature retinal aging.

Vision requires the transport and recycling of the pigment 11-cis retinaldehyde (retinal) between the retinal pigment epithelium (RPE) and photoreceptors. 11-cis retinal is also required for light-mediated photoreceptor death in dark-adapted mouse eye, probably through overstimulation of rod cells adapted for low light. Retbindin is a photoreceptor-specific protein, of unclear function, that is localized between the RPE and the tips of the photoreceptors. Unexpectedly, young Rtbdn-KO mice, with targeted deletion (KO) of retbindin, showed delayed regeneration of retinal function after bleaching and were strongly resistant to light-induced photoreceptor death. Furthermore, bio-layer interferometry binding studies showed recombinant retbindin had significant affinity for retinoids, most notably 11-cis retinal. This suggests that retbindin mediates light damage, probably through a role in transport of 11-cis retinal. In Rtbdn-KO mice, retinal development was normal, as were amplitudes of rod and cone electroretinograms (ERG) up to 4 months, although implicit times and c-waves were affected. However, with aging, both light- and dark-adapted ERG amplitudes declined significantly and photoreceptor outer segments became disordered, However, in contrast to other reports, there was little retinal degeneration or drop in flavin levels. The RPE developed vacuoles and lipid, protein and calcium deposits reminiscent of age-related macular degeneration. Other signs of premature aging included loss of OPN4+ retinal ganglion cells and activation of microglia. Thus, retbindin plays an unexpected role in the mammalian visual cycle, probably as an adaptation for vision in dim light. It mediates light damage in the dark-adapted eye, but also plays a role in light-adapted responses and in long term retinal homeostasis.

Contrast Agent Enhanced Multimodal Photoacoustic Microscopy and Optical Coherence Tomography for Imaging of Rabbit Choroidal and Retinal Vessels in vivo.

Multimodal imaging with photoacoustic microscopy (PAM) and optical coherence tomography (OCT) can be an effective method to evaluate the choroidal and retinal microvasculature. To improve the efficiency for visualizing capillaries, colloidal gold nanoparticles (AuNPs) have been applied as a multimodal contrast agent for both OCT and PAM imaging by taking advantage of the strong optical scattering and the strong optical absorption of AuNPs due to their surface plasmon resonance. Ultra-pure AuNPs were fabricated by femtosecond laser ablation, capped with polyethylene glycol (PEG), and administered to 13 New Zealand white rabbits and 3 Dutch Belted pigmented rabbits. The synthesized PEG-AuNPs (20.0 ± 1.5 nm) were demonstrated to be excellent contrast agents for PAM and OCT, and do not demonstrate cytotoxicity to bovine retinal endothelial cells in cell studies. The image signal from the retinal and choroidal vessels in living rabbits was enhanced by up to 82% for PAM and up to 45% for OCT, respectively, by the administered PEG-AuNPs, which enables detection of individual blood vessels by both imaging modalities. The biodistribution study demonstrated the AuNP accumulated primarily in the liver and spleen. Histology and TUNEL staining did not indicate cell injury or death in the lung, liver, kidney, spleen, heart, or eyes up to seven days after AuNP administration. PEG-AuNPs offer an efficient and safe contrast agent for multimodal ocular imaging to achieve improved characterization of microvasculature.