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Effect of αvβ3 Integrin Expression and Activity on Intraocular Pressure

Jennifer A Faralli1, Mark S Filla1, Donna M Peters1,2

  • 1Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, United States.

Investigative Ophthalmology & Visual Science
|April 26, 2019
PubMed
Abstract

Insights

This study shows that alpha-v beta-3 (αvβ3) integrin plays a key role in regulating intraocular pressure (IOP). Reducing αvβ3 integrin lowers IOP, while activating it increases IOP and reduces ocular outflow facility.

Area of Science:

  • Ophthalmology
  • Integrin Signaling
  • Glaucoma Research

Background:

  • Intraocular pressure (IOP) is a critical factor in glaucoma pathogenesis.
  • The role of specific integrins, such as αvβ3, in regulating IOP is not fully understood.

Purpose of the Study:

  • To investigate the impact of αvβ3 integrin expression and activation on intraocular pressure (IOP).
  • To elucidate the function of αvβ3 integrin in ocular tissues relevant to IOP regulation.

Main Methods:

  • Utilized a tamoxifen-inducible Cre-loxP system in mice to delete the β3 integrin subunit in the anterior segment.
  • Measured IOP using rebound tonometry and assessed β3 integrin expression via Western blotting and immunofluorescence.
  • Employed porcine organ culture anterior segments (POCAS) and C57BL/6J mice to study the effects of αvβ3 integrin activation using specific antibodies.

Main Results:

  • Deletion of β3 integrin subunit led to significantly lower IOP in mice, a sustained effect for 11 weeks.
  • Activation of αvβ3 integrin with the AP5 antibody significantly increased IOP in mice.
  • αvβ3 integrin activation decreased outflow facility in 42% of POCAS studied.

Conclusions:

  • αvβ3 integrin signaling is demonstrated to be a significant regulator of intraocular pressure (IOP).
  • Targeting αvβ3 integrin may offer a novel therapeutic strategy for managing IOP in ocular diseases.

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