Formation of amyloid-like fibrillar structures and destruction of fibroblasts of the Tenon's capsule in progressive myopia due to resistance of the pigment epithelium-derived factor to restricted proteolysis

We have previously shown that, normally, two forms of the pigment epithelium-derived factor (PEDF) with molecular weights of 50 and 45 kDa are present in the Tenon's capsule in equal amounts. These forms represent the full-length protein and a product of restricted proteolysis of PEDF. In persons with myopia, the full-length uncleaved factor was predominantly detected, which correlated with the disturbance of collagen fiber formation. An immunohistochemical study of the Tenon's capsule using polyclonal antibodies to PEDF showed that, in the control group, the factor is localized solely inside fibroblasts, whereas in patients with myopia, PEDF is distributed outside the cell as a halo around destroyed fibroblasts. It was shown in the present work using atomic force microscopy and immunodot assay with antibodies specific to amyloid fibrils that only the full-length PEDF is capable of forming amyloid-like fibrillar structures. The accumulation of fibrils leads to the destruction of fibroblasts and is a cause of changes in the biochemical composition and morphological structure of the Tenon's capsule in myopia. © Pleiades Publishing, Ltd., 2012.

Minkevich N.I.1 , Rakitina T.V.1, 2 , Bogachuk A.P.1 , Radchenko V.V.1 , Surina E.A.1 , Morozova-Roche L.A.3 , Yanamandra K.3 , Iomdina E.N.4 , Babichenko I.I. 5 , Kostanyan I.A.1 , Lipkin V.M.1
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  • 1 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997, Russian Federation
  • 2 Research Center Kurchatov Institute, pl. Akademika Kurchatova 1, Moscow, 123182, Russian Federation
  • 3 Department of Medical Biochemistry and Biophysics, Umeå University, SE-90187, Umeå, Sweden
  • 4 Helmholtz Moscow Research Institute of Eye Diseases, ul. Sadovaya-Chernogryazskaya 14/19, Moscow, 105062, Russian Federation
  • 5 Peoples' Friendship University of Russia, ul. Miklukho-Maklaya 6, Moscow, 117198, Russian Federation
Fibrils; Fibroblast; Myopia; Pigment epithelium-derived factor (PEDF)
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