Autoantibody against transient receptor potential M1 cation channels of retinal ON bipolar cells in paraneoplastic vitelliform retinopathy
Tóm tắt
Paraneoplastic retinopathy is caused by the cross-reaction of neoplasm-directed autoantibodies against retinal antigens and results in retinal damage. Paraneoplastic vitelliform retinopathy, a presumed paraneoplastic retinopathy with features of atypical melanoma-associated retinopathy, has recently been reported in patients with metastatic melanoma. Ocular ultrastructure and its autoantibody localization of paraneoplastic vitelliform retinopathy are still indefinable. This is the first report of anti-transient receptor potential M1 antibody directly against human retinal bipolar dendritic tips in a melanoma patient with paraneoplastic vitelliform retinopathy. We present a pair of postmortem eyes of an 80-year-old male with metastatic cutaneous melanoma, who developed paraneoplastic vitelliform retinopathy. The autopsied eyes were examined with light microscopy, immunohistochemistry, and transmission electron microscopy. Microscopically, the inner nuclear layer and outer plexiform layer were the most affected retinal structures, with local thinning. The lesions extended to the outer nuclear layer, resulting in focal retinal degeneration, edema, and atrophy. No active inflammation or melanoma cells were observed. Immunohistochemistry showed tightly compact bipolar cell nuclei (protein kinase C alpha/calbindin positive) with blur/loss of ON bipolar cell dendritic tips (transient receptor potential M1 positive) in diffusely condensed outer plexiform layer. The metastatic melanoma cells in his lung also showed immunoreactivity against transient receptor potential M1 antibody. Transmission electron microscopy illustrated degenerated inner nuclear layer with disintegration of cells and loss of cytoplasmic organelles. These cells contained many lysosomal and autophagous bodies and damaged mitochondria. Their nuclei appeared pyknotic and fragmentary. The synapses in the outer plexiform layer were extensively degenerated and replaced with empty vacuoles and disintegrated organelles. This case provides a convincing histological evidence of melanoma-associated autoantibodies directly against transient receptor potential M1 channels that target the ON bipolar cell structures in the inner nuclear and outer plexiform layers in paraneoplastic vitelliform retinopathy.
Tài liệu tham khảo
Heckenlively JR, Ferreyra HA: Autoimmune retinopathy: a review and summary. Semin Immunopathol. 2008, 30 (2): 127-134. 10.1007/s00281-008-0114-7.
Alabduljalil T, Behbehani R: Paraneoplastic syndromes in neuro-ophthalmology. Curr Opin Ophthalmol. 2007, 18 (6): 463-469. 10.1097/ICU.0b013e3282f0b497.
Kobayashi M, Ikezoe T, Uemura Y, Takeuchi T, Ueno H, Ohtsuki Y, Taguchi H: Establishment of a novel small cell lung carcinoma cell line with specific recoverin expression from a patient with cancer-associated retinopathy. Lung Cancer. 2007, 56 (3): 319-326. 10.1016/j.lungcan.2007.01.030.
Khan N, Huang JJ, Foster CS: Cancer associated retinopathy (CAR): An autoimmune-mediated paraneoplastic syndrome. Semin Ophthalmol. 2006, 21 (3): 135-141. 10.1080/08820530500350662.
Honnorat J, Antoine JC: Paraneoplastic neurological syndromes. Orphanet J Rare Dis. 2007, 2: 22-10.1186/1750-1172-2-22.
Keltner JL, Thirkill CE, Yip PT: Clinical and immunologic characteristics of melanoma-associated retinopathy syndrome: eleven new cases and a review of 51 previously published cases. J Neuroophthalmol. 2001, 21 (3): 173-187. 10.1097/00041327-200109000-00004.
Zacks DN, Pinnolis MK, Berson EL, Gragoudas ES: Melanoma-associated retinopathy and recurrent exudative retinal detachments in a patient with choroidal melanoma. Am J Ophthalmol. 2001, 132 (4): 578-581. 10.1016/S0002-9394(01)01086-8.
Nieuwendijk TJ, Hooymans JM: Paraneoplastic vitelliform retinopathy associated with metastatic choroidal melanoma. Eye (Lond). 2007, 21 (11): 1436-1437. 10.1038/sj.eye.6702949.
Lu Y, Jia L, He S, Hurley MC, Leys MJ, Jayasundera T, Heckenlively JR: Melanoma-associated retinopathy: a paraneoplastic autoimmune complication. Arch Ophthalmol. 2009, 127 (12): 1572-1580. 10.1001/archophthalmol.2009.311.
Sotodeh M, Paridaens D, Keunen J, van Schooneveld M, Adamus G, Baarsma S: Paraneoplastic vitelliform retinopathy associated with cutaneous or uveal melanoma and metastases. Klin Monbl Augenheilkd. 2005, 222 (11): 910-914. 10.1055/s-2005-858840.
Grunwald L, Kligman BE, Shields CL: Acute exudative polymorphous paraneoplastic vitelliform maculopathy in a patient with carcinoma, not melanoma. Arch Ophthalmol. 2011, 129 (8): 1104-1106. 10.1001/archophthalmol.2011.215.
Koreen L, He SX, Johnson MW, Hackel RE, Khan NW, Heckenlively JR: Anti-retinal pigment epithelium antibodies in acute exudative polymorphous vitelliform maculopathy: a new hypothesis about disease pathogenesis. Arch Ophthalmol. 2011, 129 (1): 23-29. 10.1001/archophthalmol.2010.316.
Bianciotto C, Shields CL, Thirkill CE, Materin MA, Shields JA: Paraneoplastic retinopathy with multiple detachments of the neurosensory retina and autoantibodies against interphotoreceptor retinoid binding protein (IRBP) in cutaneous melanoma. Br J Ophthalmol. 2010, 94 (12): 1684-1685. 10.1136/bjo.2008.151480. 1696
Eksandh L, Adamus G, Mosgrove L, Andreasson S: Autoantibodies against bestrophin in a patient with vitelliform paraneoplastic retinopathy and a metastatic choroidal malignant melanoma. Arch Ophthalmol. 2008, 126 (3): 432-435. 10.1001/archopht.126.3.432.
Palmowski AM, Haus AH, Pfohler C, Reinhold U, Allgayer R, Tilgen W, Ruprecht KW, Thirkill CE: Bilateral multifocal chorioretinopathy in a woman with cutaneous malignant melanoma. Arch Ophthalmol. 2002, 120 (12): 1756-1761.
Aronow ME, Adamus G, Abu-Asab M, Wang Y, Chan CC, Singh AD: Paraneoplastic Vitelliform Retinopathy: Clinicopathologic Correlation and Review of the Literature. Surv Ophthalmol. 2012, 57 (6): 558-564. 10.1016/j.survophthal.2012.02.004.
Erickson LA, Letts GA, Shah SM, Shackelton JB, Duncan LM: TRPM1 (Melastatin-1/MLSN1) mRNA expression in Spitz nevi and nodular melanomas. Mod Pathol. 2009, 22 (7): 969-976. 10.1038/modpathol.2009.56.
Duncan LM, Deeds J, Cronin FE, Donovan M, Sober AJ, Kauffman M, McCarthy JJ: Melastatin expression and prognosis in cutaneous malignant melanoma. J Clin Oncol. 2001, 19 (2): 568-576.
Miller AJ, Du J, Rowan S, Hershey CL, Widlund HR, Fisher DE: Transcriptional regulation of the melanoma prognostic marker melastatin (TRPM1) by MITF in melanocytes and melanoma. Cancer Res. 2004, 64 (2): 509-516. 10.1158/0008-5472.CAN-03-2440.
Bellone RR, Brooks SA, Sandmeyer L, Murphy BA, Forsyth G, Archer S, Bailey E, Grahn B: Differential gene expression of TRPM1, the potential cause of congenital stationary night blindness and coat spotting patterns (LP) in the Appaloosa horse (Equus caballus). Genetics. 2008, 179 (4): 1861-1870. 10.1534/genetics.108.088807.
Kim DS, Ross SE, Trimarchi JM, Aach J, Greenberg ME, Cepko CL: Identification of molecular markers of bipolar cells in the murine retina. J Comp Neurol. 2008, 507 (5): 1795-1810. 10.1002/cne.21639.
Morgans CW, Zhang J, Jeffrey BG, Nelson SM, Burke NS, Duvoisin RM, Brown RL: TRPM1 is required for the depolarizing light response in retinal ON-bipolar cells. Proc Natl Acad Sci USA. 2009, 106 (45): 19174-19178. 10.1073/pnas.0908711106.
Klooster J, Blokker J, Ten Brink JB, Unmehopa U, Fluiter K, Bergen AA, Kamermans M: Ultrastructural localization and expression of TRPM1 in the human retina. Invest Ophthalmol Vis Sci. 2011, 52 (11): 8356-8362. 10.1167/iovs.11-7575.
Koike C, Obara T, Uriu Y, Numata T, Sanuki R, Miyata K, Koyasu T, Ueno S, Funabiki K, Tani A, Ueda H, Kondo M, Mori Y, Tachibana M, Furukawa T: TRPM1 is a component of the retinal ON bipolar cell transduction channel in the mGluR6 cascade. Proc Natl Acad Sci USA. 2010, 107 (1): 332-337. 10.1073/pnas.0912730107.
Koike C, Numata T, Ueda H, Mori Y, Furukawa T: TRPM1: a vertebrate TRP channel responsible for retinal ON bipolar function. Cell Calcium. 2010, 48 (2–3): 95-101.
Audo I, Kohl S, Leroy BP, Munier FL, Guillonneau X, Mohand-Said S, Bujakowska K, Nandrot EF, Lorenz B, Preising M, Kellner U, Renner AB, Bernd A, Antonio A, Moskova-Doumanova V, Lancelot ME, Poloschek CM, Drumare I, Defoort-Dhellemmes S, Wissinger B, Leveillard T, Hamel CP, Schorderet DF, De Baere E, Berger W, Jacobson SG, Zrenner E, Sahel JA, Bhattacharya SS, Zeitz C: TRPM1 is mutated in patients with autosomal-recessive complete congenital stationary night blindness. Am J Hum Genet. 2009, 85 (5): 720-729. 10.1016/j.ajhg.2009.10.013.
van Genderen MM, Bijveld MM, Claassen YB, Florijn RJ, Pearring JN, Meire FM, McCall MA, Riemslag FC, Gregg RG, Bergen AA, Kamermans M: Mutations in TRPM1 are a common cause of complete congenital stationary night blindness. Am J Hum Genet. 2009, 85 (5): 730-736. 10.1016/j.ajhg.2009.10.012.
Li Z, Sergouniotis PI, Michaelides M, Mackay DS, Wright GA, Devery S, Moore AT, Holder GE, Robson AG, Webster AR: Recessive mutations of the gene TRPM1 abrogate ON bipolar cell function and cause complete congenital stationary night blindness in humans. Am J Hum Genet. 2009, 85 (5): 711-719. 10.1016/j.ajhg.2009.10.003.
Dhingra A, Fina ME, Neinstein A, Ramsey DJ, Xu Y, Fishman GA, Alexander KR, Qian H, Peachey NS, Gregg RG, Vardi N: Autoantibodies in melanoma-associated retinopathy target TRPM1 cation channels of retinal ON bipolar cells. J Neurosci. 2011, 31 (11): 3962-3967. 10.1523/JNEUROSCI.6007-10.2011.
Kondo M, Sanuki R, Ueno S, Nishizawa Y, Hashimoto N, Ohguro H, Yamamoto S, Machida S, Terasaki H, Adamus G, Furukawa T: Identification of autoantibodies against TRPM1 in patients with paraneoplastic retinopathy associated with ON bipolar cell dysfunction. PLoS One. 2011, 6 (5): e19911-10.1371/journal.pone.0019911.
Nomura A, Shigemoto R, Nakamura Y, Okamoto N, Mizuno N, Nakanishi S: Developmentally regulated postsynaptic localization of a metabotropic glutamate receptor in rat rod bipolar cells. Cell. 1994, 77 (3): 361-369. 10.1016/0092-8674(94)90151-1.
Morigiwa K, Vardi N: Differential expression of ionotropic glutamate receptor subunits in the outer retina. J Comp Neurol. 1999, 405 (2): 173-184. 10.1002/(SICI)1096-9861(19990308)405:2<173::AID-CNE3>3.0.CO;2-L.
Morgans CW, Brown RL, Duvoisin RM: TRPM1: the endpoint of the mGluR6 signal transduction cascade in retinal ON-bipolar cells. Bioessays. 2010, 32 (7): 609-614. 10.1002/bies.200900198.
Haverkamp S, Haeseleer F, Hendrickson A: A comparison of immunocytochemical markers to identify bipolar cell types in human and monkey retina. Vis Neurosci. 2003, 20 (6): 589-600. 10.1017/S0952523803206015.
Kunzevitzky NJ, Almeida MV, Goldberg JL: Amacrine cell gene expression and survival signaling: differences from neighboring retinal ganglion cells. Invest Ophthalmol Vis Sci. 2010, 51 (7): 3800-3812. 10.1167/iovs.09-4540.
Katyal S, Glubrecht DD, Li L, Gao Z, Godbout R: Disabled-1 alternative splicing in human fetal retina and neural tumors. PLoS One. 2011, 6 (12): e28579-10.1371/journal.pone.0028579.
Duquette PM, Zhou X, Yap NL, MacLaren EJ, Lu JJ, Wallace VA, Chen HH: Loss of LMO4 in the retina leads to reduction of GABAergic amacrine cells and functional deficits. PLoS One. 2010, 5 (10): e13232-10.1371/journal.pone.0013232.
Sarthy PV, Fu M: Localization of L-glutamic acid decarboxylase mRNA in cat retinal horizontal cells by in situ hybridization. J Comp Neurol. 1989, 288 (4): 593-600. 10.1002/cne.902880406.
Aartsen WM, van Cleef KW, Pellissier LP, Hoek RM, Vos RM, Blits B, Ehlert EM, Balaggan KS, Ali RR, Verhaagen J, Wijnholds J: GFAP-driven GFP expression in activated mouse Muller glial cells aligning retinal blood vessels following intravitreal injection of AAV2/6 vectors. PLoS One. 2010, 5 (8): e12387-10.1371/journal.pone.0012387.
The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2415/12/56/prepub