Abstract
Purpose
Our aim was to use molecular biological methods to study evidence of autoimmune disease in five patients with acute zonal occult outer retinopathy (AZOOR).
Methods
Ophthalmologic data and sera were collected from all patients, who underwent visual field (VF) examination, optical coherence tomography (OCT), and multifocal electroretinogram (mfERG) recording. Serum was prepared from each patient’s blood and analyzed for antiretinal antibody activity using immunohistochemistry and Western blot analysis on mouse and human retinas. We also searched for antigen proteins using mass spectrometry.
Results
Symptoms were blurred vision in three patients and VF defects in two; all had enlargement of the Mariotte blind spot by VF testing. OCT findings in areas corresponding to the scotoma revealed disruptions of junction borders between inner and outer segment lines. mfERGs amplitudes were reduced in each corresponding scotoma area. Immunohistochemical serum staining revealed the target antigen was present in all photoreceptors of the mouse sensory retina. Western blot analysis using patient serum samples revealed some possible candidate antigens. Mass spectrometry could not determine the causative antigen; however, a list of candidates was discovered.
Conclusion
We determined that AZOOR could be an autoimmune disease. All AZOOR patients tested using molecular biological methods had antiretinal antigens.
Similar content being viewed by others
References
Gass JD. Acute zonal occult outer retinopathy. Donders Lecture: The Netherlands Ophthalmological Society, Maastricht, Holland, June 19, 1992. J Clin Neuroophthalmol. 1993;13:79–97.
Gass JD, Agarwal A, Scott IU. Acute zonal occult outer retinopathy: a long-term follow-up study. Am J Ophthalmol. 2002;134:329–39.
Francis PJ, Marinescu A, Fitzke FW, Bird AC, Holder GE. Acute zonal occult outer retinopathy: towards a set of diagnostic criteria. Br J Ophthalmol. 2005;89:70–3.
Jampol LM, Becker KG. White spot syndromes of the retina: a hypothesis based on the common genetic hypothesis of autoimmune/inflammatory disease. Am J Ophthalmol. 2003;135:376–9.
Gass JD. Are acute zonal occult outer retinopathy and the white spot syndromes (AZOOR complex) specific autoimmune disease? Am J Ophthalmol. 2003;135:380–1.
Thirkill CE, FitzGerald P, Sergott RC, Roth AM, Tyler NK, Keltner JL. Cancer-associated retinopathy (CAR syndrome) with antibodies reacting with retinal, optic nerve, and cancer cells. N Engl J Med. 1989;321:1589–94.
Thirkill CE, Tait RC, Tyler NK, Roth AM, Keltner JL. The cancer-associated retinopathy antigen is a recoverin-like protein. Invest Ophthalmol Vis Sci. 1992;33:2768–72.
Heckenlively JR, Ferreyra HA. Autoimmune retinopathy: a review and summary. Semin Immunopathol. 2008;30:127–34.
Neutzner RV, Jäger M, Friedburg C, Deeg CA, Lorenz B. Blind spot enlargement syndrome in acute zonal occult outer retinopathy with detection of autoantibodies against the retinal antigens CRALBP and S-Ag. Ophthalmologe. 2011;108:1045–9.
Kitakawa T, Hayashi T, Takashina H, Mitooka K, Gekka T, Tsuneoka H. Improvement of central visual function following steroid pulse therapy in acute zonal occult outer retinopathy. Doc Ophthalmol. 2012;124:249–54.
Li D, Kishi S. Loss of photoreceptor outer segment in acute zonal occult outer retinopathy. Arch Ophthalmol. 2007;125:1194–200.
Spaide RF, Koizumi H, Freund KB. Photoreceptor outer segment abnormalities as a cause of blnd spot enlargement in acute zonal occult outer retinopathy-complex diseases. Am J Ophthalmol. 2008;146:111–20.
Jacobson SG, Morales DS, Sun XK, Feuer WJ, Cideciyan AV, Gass JD, et al. Pattern of retinal dysfunction in acute zonal occult outer retinopathy. Ophthalmology. 1995;102:1187–98.
Tang J, Stevens RA, Okada AA, Chin M, Nussenblatt RB, Chan CC. Association of antiretinal antibodies in acute annular outer retinopathy. Arch Ophthalmol. 2008;126:130–2.
Marmor MF, Yao XY, Hageman GS. Retinal adhisiveness in surgically enucleated human eyes. Retina. 1994;14:181–6.
Ames A, Nesbett FB. Pathophysiology of ischemic cell death: I. Time of onset of irreversible damage; importance of the different components of the ischemic insult. Stroke. 1983;14:219–26.
RenG Adamus G. Cellular targets of anti-alpha-enolase autoantibodies of patients with autoimmune retinpathy. J Autoimmun. 2004;23:161–7.
Adamus G, Amundson D, Seigel GM, Machnicki M. Anti-enolase-alpha autoantibodies in cancer-associated retinopathy: epitope mapping and cytotoxicity on retinal cells. J Autoimmun. 1998;11:671–7.
Ko AC, Hernandez J, Brinton JP, Faidley EA, Mugge SA, Mets MB, et al. Anti-γ-enolase autoimmune retinopathy manifesting in early childhood. Arch Ophthalmol. 2010;128:1590–5.
Roehlecke C, Schumann U, Ader M, Brunssen C, Bramke S, Morawietz H, et al. Stress reaction in outer segments of photoreceptors after blue light irradiation. PLoS One. 2013;8:e71570.
Dryja TP. Gene-based approach to human gene-phenotype correlations. Proc Natl Acad Sci USA. 1997;94:12117–21.
Spaide RF, Curcio CA. Anatomical correlates to the bands seen in the outer retina by optical coherence tomography: literature review and model. Retina. 2011;31:1609–19.
Fine HF, Spaide RF, Ryan EH Jr, Matsumoto Y, Yannuzzi LA. Acute zonal occult outer retinopathy in patients with multiple evanescent white dot syndrome. Arch Ophthalmol. 2009;127:66–70.
Levin LA, Nilsson SivFE, Ver Hoeve J, Wu S, Kaufman PL. Albert Alm’sAdler’s physiology of the eye. New York: Expert Consult Saunder; 2011.
Acknowledgments
The authors express their thanks to Keiko Hayashibe for her assistance as a research secretary.
Conflicts of interest
M. Tagami, None; W. Matsumiya, None; H. Imai, None; S. Kusuhara, None; S. Honda, None; A. Azumi, None.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Tagami, M., Matsumiya, W., Imai, H. et al. Autologous antibodies to outer retina in acute zonal occult outer retinopathy. Jpn J Ophthalmol 58, 462–472 (2014). https://doi.org/10.1007/s10384-014-0347-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10384-014-0347-z