Investigation of the distribution and morphology of macroglia cells in AD retina

Abstract

Purpose : Alzheimer’s Disease (AD) is the major form of dementia that affects more than 55 million people worldwide and causes neurodegenerative changes in the eye resulting in various visual symptoms including loss of visual acuity, visual field, color vision, and contrast sensitivity. The mechanisms involved in AD include amyloid beta (Aβ) deposition, phosphorylated tau accumulation, neuroinflammation and neurodegeneration. Astrocytes and mullers cells are resident macroglia cells in the retina that regulate the retinal metabolism including clearance of Aβ and protect the neurons from inflammatory and degenerative changes. Here, we investigated the role of retinal macroglia cells by examining their morphology and distribution in the eye tissues of AD donors and age-matched healthy donors.

Methods : Wholemount neuroretina punches, representing the mid-peripheral and central regions of the superior quadrant were obtained from age-matched AD (n=4, 72 ± 10 years) and healthy control donors (n=4, 72 ± 1 years). Macroglia cell markers, glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) were used to visualize the astrocytes and muller cells, respectively using immunofluorescence staining and confocal microscopy. A series of Z-stack images from nerve fiber layer (NFL) to outer nuclear layer (ONL) were obtained with ZEN 3.7 software. The distribution difference and morphological difference of macroglia between AD and control samples were analyzed quantitatively and qualitatively, respectively.

Results : The macroglia distribution in 4 layers of the neuroretina including NFL, ganglion cell layer (GCL), inner nuclear layer (INL), and ONL were reported. GS signal in the AD samples showed significant reduction in the NFL and ONL compared to control while no significant difference was observed in GCL and INL. GFAP signal in the AD samples showed significant reduction in the NFL compared to control while no significant difference is observed in GCL, INL, and ONL. Qualitative analysis showed more “beading” morphology of GS-positive muller cells and GFAP-positive astrocytes in AD compared to control.

Conclusions : The beading morphology may suggest degradation of the macroglia cells known as clasmatodendrosis. The abnormal morphology and altered population of the macroglia cells in the AD retina may signify functional impairment and contribute to the pathogenesis of AD in the eyes.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.