Autoimmunity: A possible factor in the development of retinal degeneration in the RCS rat

One hundred and sixteen patients with retinitis pigmentosa (RP), 64 patients with other eye diseases, and 36 control subjects with no known eye disease were examined for antiretinal autoimmune activity. Sera were screened by indirect immunofluorescence on normal donor human eye sections to detect antibodies to human retinal antigens. Forty three of 116 RP patients (37%), 21 out of 64 non-RP patients with other eye diseases (33%), and 1 out of 42 controls (2%) had antibodies reacting with donor eye retinal antigens. Lymphocytes were tested by an in vitro transformation assay to detect cell mediated immunity to retinal antigens. Sixteen RP patients (19%), 11 non-RP patients (18%), and four controls (10%) showed lymphocyte sensitisation. Autoimmune responses were detected in many degenerative ocular disorders, but it is not known if they play a contributory pathogenic role.

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“…Simplex rod-cone + 14 Simplex rod-cone + 15 Simplex rod-cone + 16 Simplex rod-cone 17 Simplex rod-cone…”

Section: Resultsmentioning

confidence: 99%

Autoimmunity in hereditary retinal degeneration. I. Basic studies.

Chant

Heckenlively

Meyers-Elliott

1985

British Journal of Ophthalmology

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“…We selected the RCS rat model of retinal degeneration because of similar pathology to human inherited retinal degeneration. Moreover, autoimmunity has long been suspected to be a factor in RCS retinal degeneration but has not been explored (Chant and Meyers-Elliott, 1982, Reid et al, 1987). We examined the natural immune responses for two retinal pathogenic autoantigens, arrestin (S-Ag) and interphotoreceptor retinoid-binding protein (IRBP), in those rats because both arrestin- and IRBP-reactive T cells, as well as specific AAbs have been found in diseased human serum (Gregerson et al, 1981, Wiggert et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

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

Kyger

Worley

Adamus

2013

Journal of Neuroimmunology

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Autoimmunity may contribute to retinal degeneration. The studies examined the evolution of autoimmune responses against retina in naïve dystrophic RCS rats over the course of retinal degeneration. We showed that anti-retinal autoantibodies and T cells are generated in response to the availability of antigenic material released from dying photoreceptor cells during retinal degeneration but with distinctive activation trends. Passive transfer of anti-retinal antibodies enhanced disease progression by disrupting the BRB, upregulating MCP-1, attracting blood macrophages into retina, and augmenting apoptotic photoreceptor cell death. Our findings directly link anti-retinal autoantibodies to activated macrophage entry and their possible role in neurodegeneration.

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“…TLR signaling in immune cells leads to ROS production, including oxidized lipids, and subsequent ET formation through PAD4. As well, PAD4 and ET have been implicated in retinal degeneration [22,46,47]. Investigation of PAD4 in the retina has focused on citrullination of Gfap and the process of gliosis, but PAD4 is also known to translocate to the nucleus and citrullinate histones to induce DNA unwinding expulsion in ET formation [48].…”

Section: Discussionmentioning

confidence: 99%

Unveiling Drivers of Retinal Degeneration in RCS Rats: Functional, Morphological, and Molecular Insights

Ahluwalia,

Du,

Martinez-Camarillo

et al. 2024

IJMS

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Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, significantly contribute to adult blindness. The Royal College of Surgeons (RCS) rat is a well-established disease model for studying these dystrophies; however, molecular investigations remain limited. We conducted a comprehensive analysis of retinal degeneration in RCS rats, including an immunodeficient RCS (iRCS) sub-strain, using ocular coherence tomography, electroretinography, histology, and molecular dissection using transcriptomics and immunofluorescence. No significant differences in retinal degeneration progression were observed between the iRCS and immunocompetent RCS rats, suggesting a minimal role of adaptive immune responses in disease. Transcriptomic alterations were primarily in inflammatory signaling pathways, characterized by the strong upregulation of Tnfa, an inflammatory signaling molecule, and Nox1, a contributor to reactive oxygen species (ROS) generation. Additionally, a notable decrease in Alox15 expression was observed, pointing to a possible reduction in anti-inflammatory and pro-resolving lipid mediators. These findings were corroborated by immunostaining, which demonstrated increased photoreceptor lipid peroxidation (4HNE) and photoreceptor citrullination (CitH3) during retinal degeneration. Our work enhances the understanding of molecular changes associated with retinal degeneration in RCS rats and offers potential therapeutic targets within inflammatory and oxidative stress pathways for confirmatory research and development.

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Autoimmunity: A possible factor in the development of retinal degeneration in the RCS rat

Cited by 17 publications

References 8 publications

Autoimmunity in hereditary retinal degeneration. I. Basic studies.

Autoimmunity in hereditary retinal degeneration. I. Basic studies.

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

Unveiling Drivers of Retinal Degeneration in RCS Rats: Functional, Morphological, and Molecular Insights

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