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Abnormal pigment epithelium-derived factor processing in progressive myopia.

Natalya I Minkevich1, Ludmilla A Morozova-Roche2, Elena N Iomdina3

  • 1Laboratory of Hormonal Regulation Proteins, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya Street, 16/10, GSP-7, Moscow, 117997, Russian Federation.

Experimental Eye Research
|September 4, 2016
PubMed
Summary

Pigment Epithelium-Derived Factor (PEDF) processing is altered in myopia. Reduced soluble PEDF and increased insoluble forms in the eye may drive myopia progression by destabilizing ocular tissues.

Keywords:
AmyloidMyopiaPigment epithelium-derived factorProteolytic degradationTenon's capsule

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Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Biochemistry

Background:

  • Pigment Epithelium-Derived Factor (PEDF) is crucial for ocular health.
  • Reduced PEDF levels in aqueous humor are linked to complicated myopia.
  • Understanding PEDF processing in myopia is vital for therapeutic strategies.

Purpose of the Study:

  • To investigate Pigment Epithelium-Derived Factor (PEDF) processing in the Tenon's capsule of myopic patients.
  • To analyze the distribution of full-length PEDF50 and truncated PEDF45 in progressive myopia.
  • To correlate PEDF alterations with the biomechanical changes in myopia.

Main Methods:

  • Analysis of soluble and insoluble PEDF fractions from Tenon's capsule using SDS-PAGE.
  • Enzyme-linked immunosorbent assay (ELISA) to monitor ex vivo PEDF degradation.
  • Quantitative PCR (qPCR) for PEDF mRNA expression and immunohistochemistry for PEDF distribution.

Main Results:

  • High myopia patients showed a 2-fold decrease in soluble PEDF45 and a 4-fold increase in insoluble PEDF50 in Tenon's capsule.
  • Increased insoluble PEDF50 correlated with abrogated PEDF processing, not increased expression.
  • Immunohistochemistry revealed deposited PEDF50 aggregates in the extracellular space of myopic Tenon's capsule fibroblasts.

Conclusions:

  • Limited proteolysis of PEDF is altered or abrogated in myopia.
  • Accumulation of insoluble full-length PEDF may impair fibroblast survival and extracellular matrix integrity.
  • Altered PEDF processing contributes to scleral destabilization and myopia progression.