Müller cell degeneration and microglial dysfunction in the Alzheimer’s retina

Abstract

Amyloid beta (Aβ) deposits in the retina of the Alzheimer’s disease (AD) eye may provide a useful diagnostic biomarker for AD. This study focused on the relationship of Aβ with macroglia and microglia, as these glial cells are hypothesized to play important roles in homeostasis and clearance of Aβ in the AD retina. Significantly higher Aβ load was found in AD compared to controls, and specifically in the mid-peripheral region. AD retina showed significantly less immunoreactivity against glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) compared to control eyes. Immunoreactivity against ionized calcium binding adapter molecule-1 (IBA-1), a microglial marker, demonstrated a higher level of microgliosis in AD compared to control retina. Within AD retina, more IBA-1 immunoreactivity was present in the mid-peripheral retina, which contained more Aβ than the central AD retina. GFAP co-localized rarely with Aβ, while IBA-1 co-localized with Aβ in more layers of control than AD donor retina. These results suggest that dysfunction of the Müller and microglial cells may be key features of the AD retina.

Retinal arterial Aβ40 deposition is linked with tight junction loss and cerebral amyloid angiopathy in MCI and AD patients

“…Further canonical pathway analyses pointed toward upregulations of crucial pro‐inflammatory cytokine signaling pathways that could be involved in vascular remodeling and degeneration; 44,45 this includes IL‐1, IL‐6, IL‐8, integrin, and IL‐8 signaling pathways. Indeed, previous studies have reported increased cytokine production and microglial activation in the brains of AD patients and animal models 21,41,46,47 . Together with our findings, these data further indicate that retinal inflammation occurs in parallel to brain inflammation in AD.…”

“…Along with recent progress in retinal amyloid imaging, hyperspectral imaging, fundoscopy, and optical coherence tomography‐angiography in AD patients, 11‐16 the retina has become a new direction for early or pre‐symptomatic AD screening at high spatial resolution and specificity. To date, a broad array of AD pathologies have been demonstrated in the retinas of mild cognitive impairment (MCI) and AD patients, including vascular dysfunctions, gliosis, Aβ plaques and vascular Aβ 40 and Aβ 42 deposits, abnormal tau accumulation, and neurodegeneration 8,11,12,14,17‐22,23 . Our recent work in retinas from patients with MCI and AD dementia revealed early and progressive pericyte loss along with vascular Aβ accumulation; these were associated with the severity of brain‐regional Aβ plaque, CAA, and cognitive deficit 24 .…”

Traumatic brain injury induced microglial and Caspase3 activation in the retina

“…In the GFAP+ population, the cells’ nuclei were co-labeled with Casp3, and we were able to visualize subcellular granular Casp3+ labeling colocalized with Iba1. As GFAP labels the astrocytes, and Iba1 the MGs in the retina [50, 51], we identified them as the most affected population in both TBI models. However, the differential labels in the two cell populations may indicate that Casp3 might have different effects on them.…”

Traumatic Brain Injury Induced Microglial and Caspase3 Activation in the Retina

“…In the GFAP+ population, the cells' nuclei were co-labeled with Casp3, and we were able to visualize subcellular granular Casp3+ labeling colocalized with Iba1. As GFAP labels the astrocytes, and Iba1 the MGs in the retina [42,43], we identified them as the most affected population in both TBI models. However, the differential labels in the two cell populations may indicate that Casp3 might have different effects on them.…”