Antigenicity and immunogenicity of allogeneic retinal transplants

Anosova, Natalie G.; Illigens, Ben; Boisgerault, Florence; Fedoseyeva, Eugenia V.; Young, Michael J.; Bénichou, Gilles

doi:10.1172/jci12204

Cited by 12 publications

(4 citation statements)

References 52 publications

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“…Allogeneic neuroretinal transplants can survive for several months without immunosuppression. 69,70 However, upregulation of MHC class II expression on donor microglial cells 27,28 and induction of potent T-cell responses to donor antigens 29 have been observed. We observed MHC-II expression on transplantation, but neither after sham surgery nor within the intact retinas of wild-type and rd1 mice.…”

Section: Sn and Retinal Transplantationmentioning

confidence: 99%

“…Several studies have explored the use of various cell types (e.g., neuroretinal cells, retinal pigment epithelial cells, brain and retinal precursors, and Schwann cells) in retinal transplantation approaches aimed at slowing down the progression of the degenerative process or reconstructing the degenerating retina. [22][23][24][25][26] Although intraocular grafts are seen to thrive for relatively long periods, it is clear that host immune responses are triggered, [27][28][29] ultimately limiting the survival and function of the grafts.…”

mentioning

confidence: 99%

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Sialoadhesin Expression in Intact Degenerating Retinas and Following Transplantation

Sancho‐Pelluz

Wunderlich²,

Rauch

et al. 2008

Invest. Ophthalmol. Vis. Sci.

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The significant activation of microglia/macrophages observed in the various stages of degeneration in rd1 and rds mouse retinas is not accompanied by Sn expression. However, Sn-expressing cells are observed after transplantation. The occurrence of such cells could be of significance for the integration and long-term survival of retinal grafts, as the expression of Sn could facilitate other phagocytic receptors.

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Section: Sn and Retinal Transplantationmentioning

confidence: 99%

mentioning

confidence: 99%

Sialoadhesin Expression in Intact Degenerating Retinas and Following Transplantation

Sancho‐Pelluz

Wunderlich²,

Rauch

et al. 2008

Invest. Ophthalmol. Vis. Sci.

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“…Although there were few IBA1/CD4-double positive macrophages (anti-inflammatory M2 healing macrophages), acquired immune response (CD4 and CD8) was about absent 60 days post-transplantation in WTC UDC -grafted eyes ( Fig. S10A-D) 76,77 .…”

Section: Resultsmentioning

confidence: 99%

Sub-retinal transplantation of human iPSC-derived retinal sheets: A promising approach for the treatment of macular degeneration

Barabino,

Mellal,

Hamam

et al. 2023

Preprint

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Retinal degenerative diseases affect millions of people worldwide, and legal blindness is generally associated with the loss of cone photoreceptors located in the retina's central region called the macula. Currently, there is no treatment to replace the macula. Addressing this unmet need, we employed control isogenic and hypoimmunogenic induced pluripotent stem cell (iPSC) lines to generate spontaneously polarized retinal sheets (RSs). They presented the advantage of facile customization and large-scale production, exhibiting a polarized 3D architecture within a 2D cell culture environment, thus readily adaptable for clinical applications. RSs were enriched in retinal progenitor and cone precursor cells, which could differentiate into mature S- and M/L- cones in long-term cultures. Single-cell RNA-seq analysis showed that RSs recapitulate the ontogeny of the developing human retina and are devoid of pluripotent stem cells. Isolation of neural rosettes for sub-retinal transplantation effectively eliminated unwanted cells such as RPE cells. In a porcine model of chemically induced retinal degeneration, grafts integrated the host retina and formed a new, yet immature, photoreceptor layer, exhibiting viability for up to 2 months. In one transplanted animal that met all criteria, including correct apicobasal orientation and seamless graft integration, functional and immunohistochemical assays suggest that grafts exhibited responsiveness to light stimuli and established putative synaptic connections with host bipolar neurons. This study underscores the potential and challenges of iPSC-derived RS for clinical applications while establishing the optimal methodology and conditions for RS transplantation, thus paving the path for future long-term functional investigations using RS grafts.

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“…Several attempts have been made to transplant retinal tissue (Anosova et al, 2001) or cells (photoreceptor cells, West et al, 2010; Gust and Reh, 2011; RPE cells, Tezel et al, 2007) to repair damaged or degenerating retina (West et al, 2009), but only occasionally has survival and, importantly neural integration, been reported (MacLaren et al, 2006). The erroneous notion that ocular IP will promote acceptance of such grafts has been exposed by the need for immunosuppression to assist graft acceptance (West et al, 2010).…”

Section: Breaches Of Privilegementioning

confidence: 99%

Good news–bad news: the Yin and Yang of immune privilege in the eye

Forrester¹,

Xu²

2012

Front. Immun.

122

111

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The eye and the brain are prototypical tissues manifesting immune privilege (IP) in which immune responses to foreign antigens, particularly alloantigens are suppressed, and even completely inhibited. Explanations for this phenomenon are numerous and mostly reflect our evolving understanding of the molecular and cellular processes underpinning immunological responses generally. IP is now viewed as a property of many tissues and the level of expression of IP varies not only with the tissue but with the nature of the foreign antigen and changes in the limited conditions under which privilege can operate as a mechanism of immunological tolerance. As a result, IP functions normally as a homeostatic mechanism preserving normal function in tissues, particularly those with highly specialized function and limited capacity for renewal such as the eye and brain. However, IP is relatively easily bypassed in the face of a sufficiently strong immunological response, and the privileged tissues may be at greater risk of collateral damage because its natural defenses are more easily breached than in a fully immunocompetent tissue which rapidly rejects foreign antigen and restores integrity. This two-edged sword cuts its swathe through the eye: under most circumstances, IP mechanisms such as blood–ocular barriers, intraocular immune modulators, induction of T regulatory cells, lack of lymphatics, and other properties maintain tissue integrity; however, when these are breached, various degrees of tissue damage occur from severe tissue destruction in retinal viral infections and other forms of uveoretinal inflammation, to less severe inflammatory responses in conditions such as macular degeneration. Conversely, ocular IP and tumor-related IP can combine to permit extensive tumor growth and increased risk of metastasis thus threatening the survival of the host.

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Antigenicity and immunogenicity of allogeneic retinal transplants

Cited by 12 publications

References 52 publications

Sialoadhesin Expression in Intact Degenerating Retinas and Following Transplantation

Sialoadhesin Expression in Intact Degenerating Retinas and Following Transplantation

Sub-retinal transplantation of human iPSC-derived retinal sheets: A promising approach for the treatment of macular degeneration

Good news–bad news: the Yin and Yang of immune privilege in the eye

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