Serum autoantibodies to optic nerve head glycosaminoglycans in patients with glaucoma

Gülgün Tezel, Deepak P. Edward, Martin B. Wax

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

Background: Serum autoantibodies that cross-react with glycosaminoglycans have been proposed to play a significant role in specific tissue injury in patients with systemic autoimmune diseases. Objective: To investigate whether serum immunoreactivity to glycosaminoglycans is present in patients with glaucoma who have aberrant serum autoantibodies to DNA, RNA, nuclear proteins, or retinal proteins, as proteoglycans and their glycosaminoglycan side chains are important components of the optic nerve head and its vasculature. Methods: We performed Western blotting using patient serum samples and human optic nerve head homogenates that were treated with or without specific glycosaminoglycan degrading enzymes. Monoclonal antibodies that recognize different determinants of glycosaminoglycans were used to identify specific substrate antigenicity. We compared the serum immunoreactivity to glycosaminoglycans in 60 age-matched patients with normal-pressure glaucoma, 36 patients with primary open-angle glaucoma, and 20 control subjects by enzyme-linked immunosorbent assay. In addition, immunohistochemistry was performed to compare the distribution patterns of glycosaminoglycans in the optic nerve head of postmortem eyes of age-matched patients with normal-pressure glaucoma, primary open-angle glaucoma, and control subjects. Results: Western blotting demonstrated that serum samples from patients with glaucoma who have circulating autoantibodies can recognize optic nerve head proteoglycans, including chondroitin sulfate and heparan sulfate. The level of serum autoantibodies binding purified chondroitin sulfate and heparan sulfate glycosaminoglycans in an enzyme- linked immunosorbent assay was approximately 100% higher in patients with normal-pressure glaucoma than that in control subjects and approximately 50% higher than that in patients with primary open-angle glaucoma. We also observed increased immunostaining of glycosaminoglycans in the optic nerve head of eyes with glaucoma, particularly those with normal intraocular pressure, compared with control eyes. Conclusion: There are increased levels of autoantibodies recognizing glycosaminoglycans of the optic nerve head in the serum samples of some patients with glaucoma. Clinical Relevance: These autoantibodies may increase the susceptibility of the optic nerve head to damage in these patients by changing the functional properties of the lamina cribrosa, its vasculature, or both.

Original languageEnglish (US)
Pages (from-to)917-924
Number of pages8
JournalArchives of Ophthalmology
Volume117
Issue number7
StatePublished - Jul 1999

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Optic Disk
Glycosaminoglycans
Glaucoma
Autoantibodies
Serum
Heparitin Sulfate
Pressure
Western Blotting
Enzyme-Linked Immunosorbent Assay
Chondroitin Sulfate Proteoglycans
Chondroitin Sulfates
Proteoglycans
Nuclear Proteins
Intraocular Pressure
Autoimmune Diseases
Immunohistochemistry
Monoclonal Antibodies
RNA

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Serum autoantibodies to optic nerve head glycosaminoglycans in patients with glaucoma. / Tezel, Gülgün; Edward, Deepak P.; Wax, Martin B.

In: Archives of Ophthalmology, Vol. 117, No. 7, 07.1999, p. 917-924.

Research output: Contribution to journalArticle

Tezel, Gülgün ; Edward, Deepak P. ; Wax, Martin B. / Serum autoantibodies to optic nerve head glycosaminoglycans in patients with glaucoma. In: Archives of Ophthalmology. 1999 ; Vol. 117, No. 7. pp. 917-924.
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abstract = "Background: Serum autoantibodies that cross-react with glycosaminoglycans have been proposed to play a significant role in specific tissue injury in patients with systemic autoimmune diseases. Objective: To investigate whether serum immunoreactivity to glycosaminoglycans is present in patients with glaucoma who have aberrant serum autoantibodies to DNA, RNA, nuclear proteins, or retinal proteins, as proteoglycans and their glycosaminoglycan side chains are important components of the optic nerve head and its vasculature. Methods: We performed Western blotting using patient serum samples and human optic nerve head homogenates that were treated with or without specific glycosaminoglycan degrading enzymes. Monoclonal antibodies that recognize different determinants of glycosaminoglycans were used to identify specific substrate antigenicity. We compared the serum immunoreactivity to glycosaminoglycans in 60 age-matched patients with normal-pressure glaucoma, 36 patients with primary open-angle glaucoma, and 20 control subjects by enzyme-linked immunosorbent assay. In addition, immunohistochemistry was performed to compare the distribution patterns of glycosaminoglycans in the optic nerve head of postmortem eyes of age-matched patients with normal-pressure glaucoma, primary open-angle glaucoma, and control subjects. Results: Western blotting demonstrated that serum samples from patients with glaucoma who have circulating autoantibodies can recognize optic nerve head proteoglycans, including chondroitin sulfate and heparan sulfate. The level of serum autoantibodies binding purified chondroitin sulfate and heparan sulfate glycosaminoglycans in an enzyme- linked immunosorbent assay was approximately 100{\%} higher in patients with normal-pressure glaucoma than that in control subjects and approximately 50{\%} higher than that in patients with primary open-angle glaucoma. We also observed increased immunostaining of glycosaminoglycans in the optic nerve head of eyes with glaucoma, particularly those with normal intraocular pressure, compared with control eyes. Conclusion: There are increased levels of autoantibodies recognizing glycosaminoglycans of the optic nerve head in the serum samples of some patients with glaucoma. Clinical Relevance: These autoantibodies may increase the susceptibility of the optic nerve head to damage in these patients by changing the functional properties of the lamina cribrosa, its vasculature, or both.",
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