Are Anti-Retinal Autoantibodies a Cause or a Consequence of Retinal Degeneration in Autoimmune Retinopathies?

Abstract

Autoantibodies (AAbs) against various retinal proteins have been associated with vision loss in paraneoplastic and non-paraneoplastic autoimmune retinopathies (AR). There are two major paraneoplastic syndromes associated anti-retinal AAbs, cancer-associated retinopathy (CAR), and melanoma-associated retinopathy. Some people without a cancer diagnosis may present symptoms of CAR and have anti-retinal AAbs. The etiology and pathogenesis of those entities are not fully understood. In this review, we provide evidence for the role of AAbs in retinal death and degeneration. Studies of epitope mapping for anti-recoverin, anti-enolase, and anti-carbonic anhydrase II revealed that although patients’ AAbs may recognize the same retinal protein as normal individuals they bind to different molecular domains, which allows distinguishing between normal and diseased AAbs. Given the great diversity of anti-retinal AAbs, it is likely some antibodies have greater pathogenic potential than others. Pathogenic, but not normal antibodies penetrate the target cell, reach their specific antigen, induce apoptosis, and impact retinal pathophysiology. Photoreceptors, dying by apoptosis, induced by other than immunologic mechanisms produce substantial amounts of metabolic debris, which consequently leads to autoimmunization and enhanced permeability of the blood–retinal barrier. AAbs that were made as a part of anti-cancer response are likely to be the cause of retinal degeneration, whereas others, generated against released antigens from damaged retina, contribute to the progression of retinopathy. Altogether, AAbs may trigger retinal degeneration and may also exacerbate the degenerative process in response to the release of sequestered antigens and influence disease progression.

Using bioinformatic protein sequence similarity to investigate if SARS CoV-2 infection could cause an ocular autoimmune inflammatory reactions?

“…Autoimmune retinopathies (AIRs) comprise a wide spectrum of retinal degenerative disorders that includes the paraneoplastic and non-paraneoplastic AIRs ( Adamus, 2018 ; Adamus et al, 2004 , diagnosis, ). The pathology of AIRs involves sequence similarities between retinal antigens and foreign antigens that enter the body.…”

Non-paraneoplastic autoimmune retinopathy: multimodal testing characteristics of 13 cases

“…This also supports a more recent hypothesis, according to which the development of retinopathy is due to a largely different (hereditary) mechanism, where apoptosis of photoreceptors triggers the release of antigens and the ultimate development of ARAs. Lastly, given that all five patients had concomitant autoimmune diseases and such conditions can be associated with the development of autoantibodies, it is possible that the positive blood sample results from our patients could be secondary to cross-reactivity with systemic disease autoantibodies [16].…”

Anti-retinal autoantibodies in myopic macular degeneration: a pilot study

“…There is evidence for the presence of anti-retinal autoantibodies (ARAs) in association with several retinal diseases as such geographic atrophy, age-related macular degeneration (AMD), autoimmune retinopathy and inherited retinal degeneration [6][7][8][9][10][11][12]. It has been shown in AMD that the choriocapillaris and the retinal pigment epithelium (RPE) are targets of antibody-mediated complement deposition.…”