Retinal synthesis and deposition of complement components induced by ocular hypertension

Markus H. Kuehn, Chan Y. Kim, Jelena Ostojic, Micheal Bellin, Wallace L.M. Alward, Edwin M. Stone, Donald S. Sakaguchi, Sinisa D. Grozdanic, Young H. Kwon

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Abstract

Inappropriate activity of the complement cascade contributes to the pathophysiology of several neurodegenerative conditions. This study sought to determine if components of the complement cascade are synthesized in the retina following the development of ocular hypertension (OHT) and if complement accumulates in association with retinal ganglion cells. Toward this goal the gene expression levels of complement components 1qb (C1qb) and 3 (C3) were determined in the retina by quantitative polymerase chain reaction in human eyes with elevated intraocular pressure (IOP) and healthy retinal tissue as well as in a rat model of OHT induced by laser cauterization of the trabecular meshwork and episcleral veins. Immunohistochemical methods were employed to determine the sites of complement deposition in the retina and optic nerve head. Our data demonstrate that transcript levels for C1q and C3 are significantly elevated in retinae subjected to OHT, both in the animal model as well as in human eyes. Immunohistochemical analyses indicate that C1q and C3 accumulate specifically in the retinal ganglion cell layer and the nerve fiber layer. In addition, we demonstrate that the terminal complement complex, or membrane attack complex, is formed both in the human and rat model as a consequence of OHT. Complement activation, particularly formation of membrane attack complexes, has the potential to exacerbate ganglion cell death through bystander lysis or glial cell activation. The results show that complement activation occurs in the retina that has been subjected to elevated IOP, and may have implications in pathophysiology of glaucoma.

Original languageEnglish
Pages (from-to)620-628
Number of pages9
JournalExperimental Eye Research
Volume83
Issue number3
DOIs
Publication statusPublished - 2006 Sep 1

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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    Kuehn, M. H., Kim, C. Y., Ostojic, J., Bellin, M., Alward, W. L. M., Stone, E. M., Sakaguchi, D. S., Grozdanic, S. D., & Kwon, Y. H. (2006). Retinal synthesis and deposition of complement components induced by ocular hypertension. Experimental Eye Research, 83(3), 620-628. https://doi.org/10.1016/j.exer.2006.03.002