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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

Optical coherence tomography. Retinal OCT imaging demonstrating a normal retinal architecture in the peripapillary (a, b, c) and peripheral regions (d, e, f) in both age-matched B6 naïve mice and a representative nee splenocyte recipient 12 and 72 days after transfer. No evidence for acute infiltration or retinal detachments was identified through in vivo imaging. A thinning of the retinal ganglion cell layer (rgcl, including the nerve fiber layer) was not yet evident 72 days after transfer, even though at that time a slight loss of RGC is observed using histochemical approaches. However an increased reflectivity (b, c, e, f) in the rgcl was noted when nee-transfer animals and naïve mice are compared (inl: inner nuclear layer; onl: outer nuclear layer; is/os: inner and outer photoreceptor cell segments; rpe: retinal pigment epithelium)
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Fig2: Optical coherence tomography. Retinal OCT imaging demonstrating a normal retinal architecture in the peripapillary (a, b, c) and peripheral regions (d, e, f) in both age-matched B6 naïve mice and a representative nee splenocyte recipient 12 and 72 days after transfer. No evidence for acute infiltration or retinal detachments was identified through in vivo imaging. A thinning of the retinal ganglion cell layer (rgcl, including the nerve fiber layer) was not yet evident 72 days after transfer, even though at that time a slight loss of RGC is observed using histochemical approaches. However an increased reflectivity (b, c, e, f) in the rgcl was noted when nee-transfer animals and naïve mice are compared (inl: inner nuclear layer; onl: outer nuclear layer; is/os: inner and outer photoreceptor cell segments; rpe: retinal pigment epithelium)

Mentions: Optical coherence tomography (OCT) and funduscopy is routinely used in clinical ophthalmology and in animal research to detect retinal abnormalities in vivo. To test whether the damage observed in our model was related to an acute inflammation event, we imaged recipients’ retinae at several time points after splenocyte transfer. Particular attention was directed towards any signs of uveitis, such as retinal detachments, subretinal hemorrhage, or white linear lesions as described elsewhere [10]. Retinal scans and funduscopy were carried out in an independent group of nee splenocyte recipients (N = 6) 6, 12, 18, 24, 42 and 72 days after transfer and compared to naïve control mice. Retinal folds or signs of cellular infiltrates were not observed in any of the animals after transfer of immune cells, regardless of the time interval after injection. Moreover, recipient animals uniformly display an undisturbed retinal architecture and a normal appearance of the optic nerve head, even at later stages when RGC density has already begun to decline (Fig. 2).Fig. 2


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)

Optical coherence tomography. Retinal OCT imaging demonstrating a normal retinal architecture in the peripapillary (a, b, c) and peripheral regions (d, e, f) in both age-matched B6 naïve mice and a representative nee splenocyte recipient 12 and 72 days after transfer. No evidence for acute infiltration or retinal detachments was identified through in vivo imaging. A thinning of the retinal ganglion cell layer (rgcl, including the nerve fiber layer) was not yet evident 72 days after transfer, even though at that time a slight loss of RGC is observed using histochemical approaches. However an increased reflectivity (b, c, e, f) in the rgcl was noted when nee-transfer animals and naïve mice are compared (inl: inner nuclear layer; onl: outer nuclear layer; is/os: inner and outer photoreceptor cell segments; rpe: retinal pigment epithelium)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: Optical coherence tomography. Retinal OCT imaging demonstrating a normal retinal architecture in the peripapillary (a, b, c) and peripheral regions (d, e, f) in both age-matched B6 naïve mice and a representative nee splenocyte recipient 12 and 72 days after transfer. No evidence for acute infiltration or retinal detachments was identified through in vivo imaging. A thinning of the retinal ganglion cell layer (rgcl, including the nerve fiber layer) was not yet evident 72 days after transfer, even though at that time a slight loss of RGC is observed using histochemical approaches. However an increased reflectivity (b, c, e, f) in the rgcl was noted when nee-transfer animals and naïve mice are compared (inl: inner nuclear layer; onl: outer nuclear layer; is/os: inner and outer photoreceptor cell segments; rpe: retinal pigment epithelium)
Mentions: Optical coherence tomography (OCT) and funduscopy is routinely used in clinical ophthalmology and in animal research to detect retinal abnormalities in vivo. To test whether the damage observed in our model was related to an acute inflammation event, we imaged recipients’ retinae at several time points after splenocyte transfer. Particular attention was directed towards any signs of uveitis, such as retinal detachments, subretinal hemorrhage, or white linear lesions as described elsewhere [10]. Retinal scans and funduscopy were carried out in an independent group of nee splenocyte recipients (N = 6) 6, 12, 18, 24, 42 and 72 days after transfer and compared to naïve control mice. Retinal folds or signs of cellular infiltrates were not observed in any of the animals after transfer of immune cells, regardless of the time interval after injection. Moreover, recipient animals uniformly display an undisturbed retinal architecture and a normal appearance of the optic nerve head, even at later stages when RGC density has already begun to decline (Fig. 2).Fig. 2

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