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Malia Michelle Edwards, D. Scott McLeod, Imran Ahmed Bhutto, Johanna Seddon, Gerard A Lutty; Müller cell protrusions through the external limiting membrane in aged human retinas. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5840.
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© ARVO (1962-2015); The Authors (2016-present)
Müller cells span the entire thickness of the retina, making contact with all retinal cell types. They rapidly respond to injury and it has recently been suggested that they may dedifferentiate or remodel in retinal disease. Changes to Müller cell structure and function would greatly alter the retinal milieu, potentially leading to degeneration. This study investigated unusual Müller cell protrusions through the external limiting membrane (ELM) into the subretinal space of aged human retinas.
Retinal wholemounts from aged donors without retinal disease and donors with age-related macular degeneration (AMD) or retinitis pigmentosa (RP) were stained with GFAP (astrocytes and activated Müller cells) and/or vimentin (Müller cells). UEA lectin was used to label retinal vessels. Retinas were imaged with the photoreceptor side up using a Zeiss 710 Meta confocal microscope. After imaging, retinas were cryopreserved and sectioned to better visualize the Müller cells and verify that protrusions were in the subretinal space.
GFAP-positive protrusions through the ELM were observed in 60% of the retinas investigated (N=10). When retinas were stained with vimentin, all protrusions were double labeled, confirming that these are Müller cells. In some cases, thin and disorganized processes extended into the subretinal space. In other cases, multiple processes protruded through a focal region creating a funnel-like appearance. In the most extreme cases, dense membranes containing multiple layers of overlapping processes and cell bodies were observed on the subretinal surface.<br /> Only one of four control retinas had glial protrusions through the ELM. While this donor had no history of ocular disease, the Müller cells were activated and there was vascular dropout, indicating some pathology. All donors with wet AMD had extensive membranes associated with choroidal neovascularization (CNV). Both disciform scars and atrophic CNV also contained dense glial membranes. Funnel-like glial protrusions were observed in unaffected retinal regions. The other retina investigated, from a donor with RP, contained extensive subretinal glial membranes.
Müller cells extend processes through the ELM into the subretinal space during retinal degeneration. These glial protrusions may indicate the remodeling of Müller cells in response to photoreceptor damage.
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