Imaging of Macrophage-Like Cells in Living Human Retina Using Clinical OCT

Abstract

Purpose To image retinal macrophages at the vitreoretinal interface in the living human retina using a clinical optical coherence tomography (OCT) device. Methods Eighteen healthy controls and three patients with retinopathies were imaged using a clinical spectral-domain OCT. In controls, 10 sequential scans were collected at three different locations: (1) ∼9 degrees temporal to the fovea, (2) the macula, and (3) the optic nerve head (ONH). Intervisit repeatability was evaluated by imaging the temporal retina twice on the same day and 3 days later. Only 10 scans at the temporal retina were obtained from each patient. A 3-µm OCT reflectance (OCT-R) slab located above the inner limiting membrane (ILM) surface was averaged. Results In controls, ramified macrophage-like cells with regular spatial separation were visualized in the temporal and ONH OCT-R images; however, cell structures were not resolvable at the macula. Interim changes in cell position suggestive of cell translocation were observed between images collected on the same day and those collected 3 days later. There was considerable variation in cell density and nearest-neighbor distance (NND) across controls. Mean ± SD cell densities measured at the temporal and ONH were 78 ± 23 cells/mm 2 and 57 ± 16 cells/mm 2 , respectively. Similarly, mean ± SD NNDs measured at the temporal and ONH were 74.3 ± 13.3 µm and 93.3 ± 20.0 µm, respectively. Nonuniform spatial distribution and altered morphology of the cells were identified in patients with retinopathies. Conclusions Our findings showed regular spatial separation and ramified morphology of macrophage-like cells on the ILM surface with cell translocation over time in controls. Their distribution and morphology suggest an origin of macrophage-like cells such as microglia or hyalocytes.

Retinal and Brain Microglia in Multiple Sclerosis and Neurodegeneration

“…Despite this, there have also been reports of attempts of in vivo and non-invasive imaging methods in humans [127,128]. For example, Liu et al developed a multimodal adaptive optics (AO) system which combined SLO and OCT systems [127].…”

“…Although they were able to image microglia in the inner limiting membrane (ILM), these were identified by subjective visual interpretation, and the authors emphasise the need for improvement due to the lengthy process (1 hour to image) [127]. Although AOOCTs can produce high-resolution and cellular levels of imaging, this is compromised by~6-fold reduction in the field of view compared to a commercial machine [128]. For instance, Castanos et al used spectral-domain en face OCT imaging in the reflectance mode (OCT-R) to obtain larger images of the retina [128].…”

Label-free adaptive optics imaging of human retinal macrophage distribution and dynamics

“…A more recent AO-OCT study has begun to explore their longerterm migration (48). Castanos et al (16) imaged these same ILM macrophage cells in healthy controls and retinopathy patients using clinical OCT. In these early reports of human ILM macrophage imaging, extensive characterization of distribution, motility, and changes with aging and pathology were not examined.…”

“…While retinal microglia and ILM macrophages are typically defined according to the side of the ILM on which they reside (i.e., within or outside the CNS), they share similar features in terms of morphology, capability for migration, and process motility (15,16). There is also strong evidence that labeled retinal microglia exist above the ILM in both mice and nonhuman primates (NHPs) (12,17) and may be the same cells as ILM macrophages reported in the literature.…”

Progressive Photoreceptor Dysfunction and Age-Related Macular Degeneration-Like Features in rp1l1 Mutant Zebrafish

“…Mutant en face images have fewer punctae and the rows are difficult to distinguish ( Figure 5 B). Of note, some of the mutants also had large hyper-reflective blebs in their OCT images, characteristic of activated immune cells that have translocated to the outer retina [ 22 , 23 , 24 , 25 ]. Immune cell translocation is commonly seen in response to photoreceptor disease or outer retinal injury [ 22 , 25 , 26 , 27 ].…”