Transforming growth factor β2 levels in the aqueous humor in different types of glaucoma and the relation to filtering bleb development

Picht, Greda; Welge-Luessen, Ulrich; Grehn, Franz; Lütjen–Drecoll, Elke

doi:10.1007/s004170000252

Cited by 248 publications

(178 citation statements)

References 16 publications

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“…28 The TGF-b antisense OGN would be expected to have maximal effects on local cellular production of TGF-b at the filtration wound site and not in aqueous which is known to contain high concentrations of TGF-b2 protein in association with glaucoma and intraocular fibrosis. 20,[44][45][46] Aqueous TGF-b2 is produced by cells within the eye, ie in the iris, ciliary body 47 and trabecular meshwork. 48 As application of the TGF-b2 antisense OGN subconjunctivally in this rabbit study is external to the eye, it cannot directly suppress intraocular production of TGF-b2, so we can only postulate that it may reduce aqueous TGF-b2 by interfering with the TGF-b2 autoinduction pathway from the cells within the eye.…”

Section: Discussionmentioning

confidence: 99%

Novel antisense oligonucleotides targeting TGF-β inhibit in vivo scarring and improve surgical outcome

Cordeiro¹,

Mead²,

Ali

et al. 2003

Gene Ther

158

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The scarring response is an important factor in many diseases throughout the body. In addition, it is a major problem in influencing results of surgery. In the eye, for example, post-operative scarring can determine the outcome of surgery. This is particularly the case in the blinding disease glaucoma, where several anti-scarring regimens are currently used to improve glaucoma surgery results, but are of limited use clinically because of severe complications. We have recently identified transforming growth factor-b (TGF-b) as a target for post-operative anti-scarring therapy in glaucoma, and now report the first study of novel secondgeneration antisense phosphorothioate oligonucleotides against TGF-b in vivo. Single applications of a TGF-b OGN at the time of surgery in two different animal models closely related to the surgical procedure performed in glaucoma patients, significantly reduced post-operative scarring (Po0.05) and improved surgical outcome. Our findings suggest that TGF-b antisense oligonucleotides have potential as a new therapy for reducing post-surgical scarring. Its long-lasting effects after only a single administration at the time of surgery make it particularly attractive clinically. Furthermore, although we have shown this agent to be useful in the eye, it could have widespread applications anywhere in the body where the wound-healing response requires modulation.

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Section: Discussionmentioning

confidence: 99%

Novel antisense oligonucleotides targeting TGF-β inhibit in vivo scarring and improve surgical outcome

Cordeiro¹,

Mead²,

Ali

et al. 2003

Gene Ther

158

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“…Physiologically, TGFb is mainly produced in the ciliary epithelium and lens epithelium as a latent, inactive, form consisting of mature TGFb, the latency-associated peptide (LAP) (small latent form), and the latent-TGFb-binding protein (LTBP). [17][18][19][20][21][22][23][24] Heterogeneous expression patterns of each TGFb isoform in the crystalline lens have been reported in humans and animals. 25 During the clinical course of various ocular diseases, the concentration of TGFb2 in the aqueous humor changes.…”

Section: Cytokines and Growth Factors In Aqueous Humor Of The Eyementioning

confidence: 99%

TGFβ pathobiology in the eye

Saika

2006

Laboratory Investigation

239

185

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“…Our results are consistent with previous studies showing that TGF-b2 levels are higher in individuals with a glaucoma diagnosis. 9,10,12 These results, together with studies showing that TGF-b2 increases outflow resistance and IOP in ex vivo and in vivo glaucoma models, 15,16 support the idea that elevated levels of TGF-b2 contribute to the development of open-angle glaucoma.…”

mentioning

confidence: 74%

“…[6][7][8][9][10] Under normal conditions, TGF-b2 is thought to contribute to the development of immune privilege within the eye 11 ; however, several studies have provided evidence that elevated levels of TGF-b2 in aqueous humor are associated with the development of primary open-angle glaucoma. 8,9,12,13 The current studies were undertaken to investigate whether Department of Ophthalmology, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina.…”

Section: Introductionmentioning

confidence: 99%

Influence of Race and Age on Aqueous Humor Levels of Transforming Growth Factor-Beta 2 in Glaucomatous and Nonglaucomatous Eyes

Trivedi

Nutaitis

Vroman

et al. 2011

Journal of Ocular Pharmacology and Therapeutics

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Purpose: To evaluate the influence of race and age on aqueous humor levels of transforming growth factor-beta 2 (TGF-b2). Methods: Patients >40 years of age and undergoing cataract or glaucoma surgery without associated significant intraocular pathology were selected for this study. In bilateral cases, only the first operated eye was included for evaluation. At the time of surgery, a small amount of aqueous was withdrawn. The concentration of total TGFb2 was measured by enzyme-linked immunosorbent assay in duplicate by a masked observer. Results: Fifty-five aqueous humor samples were analyzed from subjects with an average age of 68.05 AE 10.94 years. Overall median TGF-b2 concentration was 247.03 pg/mL. The median concentration of TGF-b2 was higher in eyes with glaucoma than in eyes without glaucoma (269.39 vs. 165.56 pg/mL, respectively; P ¼ 0.001). Subgroup analysis found no significant difference between African American and Caucasian American subjects in the nonglaucomatous or glaucomatous subgroups. Age showed positive correlation with TGF-b2 in nonglaucomatous eyes (r 2 ¼ 0.44, P ¼ 0.019). No correlation between age and TGF-b2 was noted in the glaucoma group (r 2 ¼ 0.02, P ¼ 0.343). Conclusion:The aqueous humor concentration of TGF-b2 was significantly higher in eyes with glaucoma than in eyes without glaucoma. No significant difference between the aqueous humor levels of TGF-b2 from African American and Caucasian American subjects could be measured. However, a significant and positive correlation between age and aqueous humor concentration of TGF-b2 in the eyes of nonglaucomatous subjects was measured. These results are consistent with the idea that elevated levels of TGF-b2 within the anterior segment contribute to the development of glaucoma. In addition, the increased risk for developing glaucoma as one ages may in part be related to the rise of this cytokine.

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Transforming growth factor β2 levels in the aqueous humor in different types of glaucoma and the relation to filtering bleb development

Cited by 248 publications

References 16 publications

Novel antisense oligonucleotides targeting TGF-β inhibit in vivo scarring and improve surgical outcome

Novel antisense oligonucleotides targeting TGF-β inhibit in vivo scarring and improve surgical outcome

TGFβ pathobiology in the eye

Influence of Race and Age on Aqueous Humor Levels of Transforming Growth Factor-Beta 2 in Glaucomatous and Nonglaucomatous Eyes

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