Adoptive transfer of immune cells from glaucomatous mice provokes retinal ganglion cell loss in recipients

Oliver W Gramlich; Qiong J Ding; Wei Zhu; Amy Cook; Michael G Anderson; Markus H Kuehn

doi:10.1186/s40478-015-0234-y

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Adoptive transfer of immune cells from glaucomatous mice provokes retinal ganglion cell loss in recipients

Journal article

Open access

Peer reviewed

Adoptive transfer of immune cells from glaucomatous mice provokes retinal ganglion cell loss in recipients

Oliver W Gramlich, Qiong J Ding, Wei Zhu, Amy Cook, Michael G Anderson and Markus H Kuehn

Acta neuropathologica communications, Vol.3(1), 56

09/15/2015

DOI: 10.1186/s40478-015-0234-y

PMCID: PMC4591529

PMID: 26374513

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https://doi.org/10.1186/s40478-015-0234-yView

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Abstract

Several studies have indicated that autoimmune and neuroinflammatory processes contribute to the neurodegeneration of retinal ganglion cells in human glaucoma patients and in animal models. To test the involvement of cellular immune processes in the pathophysiology of retinal ganglion cell degeneration in vivo, we carried out adoptive transfer experiments from two independent genetic mouse models of glaucoma into normal recipient mice. Our findings indicate that transfer results in a progressive loss of retinal ganglion cells and their axons despite normal intraocular pressure in recipient mice. Signs of pan-retinal inflammation were not detected. Similar findings were obtained following transfer of isolated T-lymphocytes, but not after transfer of splenocytes from immune deficient glaucomatous mice. Transferred lymphocytes were detected integrated in the spleen and in the retinal ganglion cell layer of recipient animals, albeit at very low frequencies. Furthermore, we observed cell-cell interaction between transferred T-cells and recipient microglia along with focal microglial activation in recipient eyes. This study demonstrates that the pathophysiology of glaucomatous degeneration in the tested animal models includes T-cell mediated events that are capable of causing loss of healthy retinal ganglion cells.

Mutation

Glaucoma - etiology

Microglia - metabolism

Retina - metabolism

Cytoskeletal Proteins - genetics

Adoptive Transfer

T-Lymphocytes - transplantation

Antigens, CD - metabolism

Retinal Ganglion Cells - pathology

Intraocular Pressure - genetics

Time Factors

Microglia - pathology

Microfilament Proteins - metabolism

Eye Proteins - genetics

Disease Models, Animal

Calcium-Binding Proteins - metabolism

Glycoproteins - genetics

Tomography, Optical Coherence

Mice, Inbred C57BL

Mice, Transgenic

Lymphocytes - pathology

Animals

Phospholipid Transfer Proteins - genetics

T-Lymphocytes - immunology

Glaucoma - pathology

Mice

Glaucoma - genetics

Retina - pathology

Details

Title: Subtitle: Adoptive transfer of immune cells from glaucomatous mice provokes retinal ganglion cell loss in recipients
Creators: Oliver W Gramlich - Center for the Prevention and Treatment of Visual Loss, Iowa City VA Health Care System, 3135C MERF, 375 Newton Road, Iowa City, IA, 52242, USA
Qiong J Ding - Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, 52242, IA, USA
Wei Zhu - Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, 52242, IA, USA
Amy Cook - Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, 52242, IA, USA
Michael G Anderson - Department of Molecular Physiology and Biophysics, The University of Iowa, Iowa City, 52242, IA, USA
Markus H Kuehn - Center for the Prevention and Treatment of Visual Loss, Iowa City VA Health Care System, 3135C MERF, 375 Newton Road, Iowa City, IA, 52242, USA. Markus-kuehn@uiowa.edu
Resource Type: Journal article
Publication Details: Acta neuropathologica communications, Vol.3(1), 56
DOI: 10.1186/s40478-015-0234-y
PMID: 26374513
PMCID: PMC4591529
NLM abbreviation: Acta Neuropathol Commun
ISSN: 2051-5960
eISSN: 2051-5960
Publisher: England
Grant note: I01 RX001163 / RRD VA EYO17673 / PHS HHS EY017142 / NEI NIH HHS R01 EY017673 / NEI NIH HHS
Language: English
Date published: 09/15/2015
Academic Unit: Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9983979954702771

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