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

Gramlich OW, Ding QJ, Zhu W, Cook A, Anderson MG, Kuehn MH - Acta Neuropathol Commun (2015)

Bottom Line: Signs of pan-retinal inflammation were not detected.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, 52242, IA, USA.

ABSTRACT

Introduction: 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.

Results: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Transferred lymphocytes infiltrate the retina and spleen. a, b Immunohistochemical detection of DsRed/CD3+ T-lymphocytes (red) derived from (a) healthy B6 (b) nee donors in the retina of recipient mice 20 days after transfer. The presence of sporadic extravasated DsRed+/CD3+ T-lymphocytes located either within the recipients’ RGC layer (shown in a) or epiretinally on the surface of the nerve fiber layer (shown in b) was noted in all recipients. V = retinal vessel. c-f Infiltration of transferred DsRed+ lymphocytes into the spleen of recipient animals 28 days after injection. Integration of immune cells obtained from nee donors was noticeably more pronounced than that of those derived from B6 donors. Notation of CD3 or CD19 in the microphotographs refers to the transferred lymphocyte fraction rather than immunohistochemical detection. DAPI was used to label nuclei
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Fig4: Transferred lymphocytes infiltrate the retina and spleen. a, b Immunohistochemical detection of DsRed/CD3+ T-lymphocytes (red) derived from (a) healthy B6 (b) nee donors in the retina of recipient mice 20 days after transfer. The presence of sporadic extravasated DsRed+/CD3+ T-lymphocytes located either within the recipients’ RGC layer (shown in a) or epiretinally on the surface of the nerve fiber layer (shown in b) was noted in all recipients. V = retinal vessel. c-f Infiltration of transferred DsRed+ lymphocytes into the spleen of recipient animals 28 days after injection. Integration of immune cells obtained from nee donors was noticeably more pronounced than that of those derived from B6 donors. Notation of CD3 or CD19 in the microphotographs refers to the transferred lymphocyte fraction rather than immunohistochemical detection. DAPI was used to label nuclei

Mentions: Consequently, it appears that transferred T-lymphocytes are able to pass the blood retina barrier and are present in the retinal parenchyma, although at a very low frequency. Furthermore, a dramatic increase in the number of extravasated lymphocytes was not apparent in mice having received adoptive transfers from glaucomatous mice. DsRed+ cells could also be detected in blood smears of all recipient mice shortly after transfer and throughout the study. Transferred DsRed+ T- and B-lymphocytes were also readily detectable in the spleens of recipient mice where they become integrated into the pulpa in all recipient groups (Fig. 4c-f).Fig. 4


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

Gramlich OW, Ding QJ, Zhu W, Cook A, Anderson MG, Kuehn MH - Acta Neuropathol Commun (2015)

Transferred lymphocytes infiltrate the retina and spleen. a, b Immunohistochemical detection of DsRed/CD3+ T-lymphocytes (red) derived from (a) healthy B6 (b) nee donors in the retina of recipient mice 20 days after transfer. The presence of sporadic extravasated DsRed+/CD3+ T-lymphocytes located either within the recipients’ RGC layer (shown in a) or epiretinally on the surface of the nerve fiber layer (shown in b) was noted in all recipients. V = retinal vessel. c-f Infiltration of transferred DsRed+ lymphocytes into the spleen of recipient animals 28 days after injection. Integration of immune cells obtained from nee donors was noticeably more pronounced than that of those derived from B6 donors. Notation of CD3 or CD19 in the microphotographs refers to the transferred lymphocyte fraction rather than immunohistochemical detection. DAPI was used to label nuclei
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4591529&req=5

Fig4: Transferred lymphocytes infiltrate the retina and spleen. a, b Immunohistochemical detection of DsRed/CD3+ T-lymphocytes (red) derived from (a) healthy B6 (b) nee donors in the retina of recipient mice 20 days after transfer. The presence of sporadic extravasated DsRed+/CD3+ T-lymphocytes located either within the recipients’ RGC layer (shown in a) or epiretinally on the surface of the nerve fiber layer (shown in b) was noted in all recipients. V = retinal vessel. c-f Infiltration of transferred DsRed+ lymphocytes into the spleen of recipient animals 28 days after injection. Integration of immune cells obtained from nee donors was noticeably more pronounced than that of those derived from B6 donors. Notation of CD3 or CD19 in the microphotographs refers to the transferred lymphocyte fraction rather than immunohistochemical detection. DAPI was used to label nuclei
Mentions: Consequently, it appears that transferred T-lymphocytes are able to pass the blood retina barrier and are present in the retinal parenchyma, although at a very low frequency. Furthermore, a dramatic increase in the number of extravasated lymphocytes was not apparent in mice having received adoptive transfers from glaucomatous mice. DsRed+ cells could also be detected in blood smears of all recipient mice shortly after transfer and throughout the study. Transferred DsRed+ T- and B-lymphocytes were also readily detectable in the spleens of recipient mice where they become integrated into the pulpa in all recipient groups (Fig. 4c-f).Fig. 4

Bottom Line: Signs of pan-retinal inflammation were not detected.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, 52242, IA, USA.

ABSTRACT

Introduction: 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.

Results: 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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus