title: Abnormal pigment epithelium-derived factor processing in progressive myopia.
abstract: Pigment Epithelium-Derived Factor (PEDF) is a secreted glycoprotein belonging to the family of non-inhibitory serpins. It is known, that in cases of complicated myopia, the content of PEDF in aqueous humor of the anterior chamber is significantly reduced. Here we examined a bulk of Tenon's capsule samples obtained from various groups of myopes, to examine PEDF processing in progressive myopia. We have analyzed the distribution of full length PEDF50 and its truncated form PEDF45 in the soluble and insoluble fractions extracted from Tenon's capsule of myopic and control (non-myopic) patients using SDS-polyacrylamide gel electrophoresis, as well as monitored the proteolytic degradation of PEDF ex vivo by enzyme-linked immunosorbent assay. These results were complemented by PEDF mRNA analysis in correspondent tissues by using qPCR and immunohistochemistry analysis of PEDF distribution in normal and myopic specimens. We found that in the Tenon's capsule of patients suffering from a high myopia the level of "soluble" 45 kDa PEDF reduced by 2-fold, while the content of "insoluble" 50 kDa form of PEDF was increased by 4-fold compared to controls. Excessive amount of PEDF50 in myopic specimens have been shown to correlate with the abrogated PEDF processing rather than with an increase of its expression. Moreover, immunohistochemical staining of the myopic Tenon's capsule tissue sections revealed the halo of deposited PEDF50 in the fibroblast extracellular space. These findings suggest that in myopia limited proteolysis of PEDF is altered or abrogated. Accumulation of full-length PEDF insoluble aggregates in the fibroblast intercellular space may affect cell survival and consequently causes the destructive changes in the extracellular matrix of the eye connective tissues. As a result, the abrogation of full-length PEDF normal processing can be an important mechanism leading to biomechanical destabilization of the scleral capsule and myopia progression.
authors: Laboratory of Hormonal Regulation Proteins, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya Street, 16/10, GSP-7, Moscow, 117997, Russian Federation. Electronic address: minkevich.natalya@gmail.com.
authors: Natalya I
authors: NI
authors: Minkevich
authors: Department of Medical Biochemistry and Biophysics, Umeå University, 901 87, Umeå SE, Umeå, Sweden.
authors: Ludmilla A
authors: LA
authors: Morozova-Roche
authors: Department of Refraction Pathology, Binocular Vision and Ophthalmoergonomics, Moscow Helmholtz Research Institute of Eye Diseases, Sadovaya-Chernogryazskaya Street, 14/19, Moscow, 105062, Russian Federation.
authors: Elena N
authors: EN
authors: Iomdina
authors: Laboratory of Hormonal Regulation Proteins, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya Street, 16/10, GSP-7, Moscow, 117997, Russian Federation; Protein Factory Division, National Research Centre "Kurchatov Institute", Akademika Kurchatova Squire, 1, Moscow, 123182, Russian Federation.
authors: Tatiana V
authors: TV
authors: Rakitina
authors: Laboratory of Hormonal Regulation Proteins, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya Street, 16/10, GSP-7, Moscow, 117997, Russian Federation.
authors: Anna P
authors: AP
authors: Bogachuk
authors: Laboratory of Hormonal Regulation Proteins, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya Street, 16/10, GSP-7, Moscow, 117997, Russian Federation.
authors: Dmitry L
authors: DL
authors: Kakuev
authors: Laboratory of Hormonal Regulation Proteins, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya Street, 16/10, GSP-7, Moscow, 117997, Russian Federation.
authors: Evgeniya V
authors: EV
authors: Smirnova
authors: Department of Pathology, Medical Faculty Peoples' Friendship University of Russia, Miklukho-Maklaya Street, 6, Moscow, 117198, Russian Federation.
authors: Igor I
authors: II
authors: Babichenko
authors: Laboratory of Hormonal Regulation Proteins, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya Street, 16/10, GSP-7, Moscow, 117997, Russian Federation.
authors: Valery M
authors: VM
authors: Lipkin
mesh_terms: D000293:Adolescent; D001082:Aqueous Humor / Q000378:metabolism; D015153:Blotting, Western; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D047728:Myopia, Degenerative / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012029:Refraction, Ocular; D015843:Serpins / Q000235:genetics* / Q000378:metabolism; D058475:Tenon Capsule / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D012313:RNA; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor
keywords: Amyloid; Myopia; Pigment epithelium-derived factor; Proteolytic degradation; Tenon's capsule