Autoimmune responses against photoreceptor antigens during retinal degeneration and their role in macrophage recruitment into retinas of RCS rats

Kyger, Madison; Worley, Aneta; Adamus, Grażyna

doi:10.1016/j.jneuroim.2012.10.007

Cited by 30 publications

(28 citation statements)

References 45 publications

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“…The sections were subsequently mounted (VECTASHIELD mounting medium with DAPI; Vector Laboratories, Inc., Burlingame, CA, USA), and visualized by confocal microscopy (LSM510; Carl Zeiss AG). The apoptotic index of the ONL was calculated as the number of TUNEL-positive nuclei / number of photoreceptor cell nuclei, as previously described by Kyger et al (25).…”

Section: Methodsmentioning

confidence: 99%

Protection of photoreceptors by intravitreal injection of the Y-27632 Rho-associated protein kinase inhibitor in Royal College of Surgeons rats

Zhang

Wei

Jiang

et al. 2015

Molecular Medicine Reports

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Retinitis pigmentosa (RP) is an inherited retinal disease, which is characteristic by degeneration of the rod and cone photoreceptors. The present study aimed to assess the protective effects on photoreceptors of intravitreal injection of Y‑27632, a specific inhibitor of Rho‑associated protein kinase (ROCK), in a Royal College of Surgeons (RCS) rat model. Different concentrations of Y‑27632 (1‑50 mM) were administered by intravitreal injection into the RCS rats. The effects of Y‑27632 were recorded using electroretinography (ERG), measuring the thicknesses of the retinal outer nuclear layer (ONL) and examination of apoptotic markers using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and western blot analysis. Treatment of the eyes with Y27632 at 10 or 50 mM, led to a 30% increase in a‑ and b‑wave amplitudes in ERG, and an increase in ONL thickness by 10%, compared with the 1 mM Y‑27632‑treated and vehicle (phosphate‑buffered saline; PBS)‑treated groups. In addition, eyes treated with 10 mM Y27632 exhibited a 90% decrease in TUNEL‑positive cells, accompanied by decreased protein expression levels of active caspase 3 and Bax by 50%, and a 90% increase in the ratio of Bcl‑2/Bax, compared with the PBS‑treated groups. These data suggested that Y‑27632 protected retinal function by inhibiting the apoptosis of photoreceptor cells in the RCS rat model. The present study demonstrated for the first time, to the best of our knowledge, to report the use of Y‑27632 for protection against RP in an RCS rat model. Y‑27632 may be a potential candidate for the treatment of human RP.

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Section: Methodsmentioning

confidence: 99%

Protection of photoreceptors by intravitreal injection of the Y-27632 Rho-associated protein kinase inhibitor in Royal College of Surgeons rats

Zhang

Wei

Jiang

et al. 2015

Molecular Medicine Reports

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“…93 However, the ability of the IgG1 and IgG3 isotypes to bind Fc receptors may have played a role in the recruitment of these monocyte/macrophage cells to the injured tissue. 53,93,94 Antiretinal antibodies can penetrate retinal cells in vitro and in vivo by the process called endocytosis. 85,86,95,96 Purified anti-recoverin or anti-enolase IgGs or their Fab fragments are equally cytotoxic for retinal cells in the presence and absence of complement, suggesting that complement does not play a major role in antibody pathogenicity.…”

Section: Evidence For Pathogenicity Of Antiretinal Autoantibodiesmentioning

confidence: 99%

Latest Updates on Antiretinal Autoantibodies Associated With Vision Loss and Breast Cancer

Adamus¹

2015

Investigative Ophthalmology & Visual Science

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Cancer-associated retinopathy (CAR) is an uncommon paraneoplastic disorder of the retina that is frequently associated with breast cancer in pre- and postmenopausal women older than 50 years. In this review, we will give an update on the current knowledge regarding the association of antiretinal autoantibodies with the breast-CAR syndrome. Women with breast cancer and visual indications of CAR have a significantly increased incidence of autoantibodies (AAbs) against retinal proteins when compared to healthy women. The onset of visual loss in association with antiretinal AAbs peaks 2 to 3 years after the clinical diagnosis of breast cancer. Differences in severity of symptoms between women with or without antiretinal AAbs are evident, revealing more unfavorable presentation in seropositive women. The incidence of CAR in breast cancer is likely to rise as the survival time of patients with breast cancer increases; consequently, a prediction of breast-CAR based on autoimmunity to individual retinal antigens, or to panels of antigens (signatures), is clinically important.

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“…People with enhanced retinal degeneration driven by mutations affecting photoreceptor viability may also be at increased risk, especially if clearance mechanisms or immune regulatory mechanisms are impaired. In an RCS rat model of retinal degeneration, Abs and T cell responses to retinal Ags arose spontaneously in unimmunized rats, possibly as a result of necrosis of photoreceptor cells (27). Once immune tolerance of T cells to recoverin, IRBP, or any other initiating autoantigen in the retina is broken, the autoimmune response may spread to other retinal proteins and, as described above, manifest as uveitis if there is a delay in diagnosis or a major impairment in immune regulation.…”

Section: Discussionmentioning

confidence: 99%

Immune Cell Infiltration into the Eye Is Controlled by IL-10 in Recoverin-Induced Autoimmune Retinopathy

Nikoopour

Lin

Sheskey

et al. 2019

The Journal of Immunology

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Autoimmune retinopathy (AIR) is a treatable condition that manifests in acute and progressive vision loss in patients. It has recently been determined that AIR is associated with an imbalance of T H 1 versus regulatory T cell immunity toward the retinal protein, recoverin. This study describes a new murine model to understand the immunopathology of AIR and its association with T cell responses toward recoverin. Immunization of C57BL/6 mice with recoverin resulted in ocular inflammation including infiltration of CD4 + and CD8 + T lymphocytes, B cells, and CD11b + Ly6C + inflammatory monocytes in the eyes. Production of IFN-g and IL-17 from T cells was exacerbated in IL-10 knockout (KO) mice and kinetics of disease development was accelerated. Infiltration of T cells and inflammatory monocytes into the eyes dramatically increased in recoverin-immunized IL-10 KO mice. An immunodominant peptide of recoverin, AG-16, was capable of inducing disease in IL-10 KO mice and resulted in expansion of AG-16 tetramer-specific CD4 + T cells in lymphoid organs and eyes. Adoptive transfer of recoverin-stimulated cells into naive mice was sufficient to induce AIR, and immunization of B cell-deficient mice led to a milder form of the disease. This model supports the hypothesis that recoverin-specific T cell responses are major drivers of AIR pathogenesis and that IL-10 is an important factor in protection.

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Autoimmune responses against photoreceptor antigens during retinal degeneration and their role in macrophage recruitment into retinas of RCS rats

Cited by 30 publications

References 45 publications

Protection of photoreceptors by intravitreal injection of the Y-27632 Rho-associated protein kinase inhibitor in Royal College of Surgeons rats

Protection of photoreceptors by intravitreal injection of the Y-27632 Rho-associated protein kinase inhibitor in Royal College of Surgeons rats

Latest Updates on Antiretinal Autoantibodies Associated With Vision Loss and Breast Cancer

Immune Cell Infiltration into the Eye Is Controlled by IL-10 in Recoverin-Induced Autoimmune Retinopathy

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