July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
HYAL4 and PH20, involved in the hydrolysis of chondroitin sulfate chains, undergo a subexpression in the cornea of keratoconus patients
Author Affiliations & Notes
  • Luis M. Quirós
    Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica & Universidad de Oviedo, Oviedo, Spain
    Department of Functional Biology, University of Oviedo, Oviedo, Spain
  • Jesus Merayo-Lloves
    Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica & Universidad de Oviedo, Oviedo, Spain
    Ophthalmology Area, Surgery Department, University of Oviedo, Oviedo, Spain
  • Ignacio Alcalde
    Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica & Universidad de Oviedo, Oviedo, Spain
  • Carla Martín
    Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica & Universidad de Oviedo, Oviedo, Spain
    Department of Functional Biology, University of Oviedo, Oviedo, Spain
  • Fernando Vázquez
    Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica & Universidad de Oviedo, Oviedo, Spain
    Department of Microbiology, Hospital Universitario Central de Asturias, Oviedo, Spain
  • Jose Alfonso
    Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica & Universidad de Oviedo, Oviedo, Spain
    Ophthalmology Area, Surgery Department, University of Oviedo, Oviedo, Spain
  • Luis Fernández-Vega
    Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica & Universidad de Oviedo, Oviedo, Spain
  • Beatriz García
    Instituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica & Universidad de Oviedo, Oviedo, Spain
    Department of Functional Biology, University of Oviedo, Oviedo, Spain
  • Footnotes
    Commercial Relationships   Luis Quirós, None; Jesus Merayo-Lloves, None; Ignacio Alcalde, None; Carla Martín, None; Fernando Vázquez, None; Jose Alfonso, None; Luis Fernández-Vega, None; Beatriz García, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 5107. doi:
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      Luis M. Quirós, Jesus Merayo-Lloves, Ignacio Alcalde, Carla Martín, Fernando Vázquez, Jose Alfonso, Luis Fernández-Vega, Beatriz García; HYAL4 and PH20, involved in the hydrolysis of chondroitin sulfate chains, undergo a subexpression in the cornea of keratoconus patients. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5107.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Glycosaminoglycan chains are essential for the structure and function of the cornea. Previously, we have described alterations in the structure of the chains of heparan sulfate (HS) and chondroitin sulfate (CS) in the cornea of keratoconus patients. The development of the pathology also produces an overexpression of the enzyme heparanase, responsible for the fragmentation of HS chains, and related to the inflammation associated with it. The objective of this work is to determine if there are alterations in the expression of the enzymes capable of hydrolyzing the chains of CS: HYAL1, HYAL4 and PH20, related to the development of the pathology.

Methods : Human central corneal tissue was obtained from cadaver donors and from penetrating keratoplasty interventions; epithelial samples were obtained by impression cytology from patients and from healthy volunteers. A transcriptomic approach was used employing quantitative polymerase chain reaction to analyze the expression of HYAL1, HYAL4 and PH20 in stromal and epithelial corneal cells. The protein expression was analyzed by immunohistochemistry in corneal sections.

Results : Transcripts for the 3 genes analyzed were detected in the corneal epithelium of healthy individuals. HYAL4 and PH20 were the most abundant species, with mRNA levels about an order of magnitude higher than HYAL1. The 3 types of transcripts were also detected in keratoconus, with no significant differences in HYAL1 with respect to the controls; however, both HYAL4 and PH20 experienced a significant decrease in their mRNA levels (p <0.05).
HYAL1 constituted the predominantly transcribed species in the corneal stroma, at levels similar to the epithelium, and without changes in keratoconus. In contrast, the levels of HYAL4 and PH20 were very low and, again, experienced a significant decrease in keratoconus.
The immunohistochemical analysis showed consistent results with the transcriptomic studies for the 3 molecules.

Conclusions : The cornea expresses the 3 enzymes known capable of hydrolyzing the CS chains, although at different levels in the epithelium and in the stroma. In keratoconus, underexpression of HYAL4 and SPAM is detected in both types of tissue. These results are related to the changes in the structure and levels of CS in the pathology and, with probability, to the physiological alterations and the inflammatory process associated with it.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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