Correlation of fibrosis and transforming growth factor-beta type 2 levels in the eye.

Connor, Thomas B.; Roberts, Anita B.; Sporn, Michael B.; Danielpour, David; Dart, Linda L.; Michels, Ronald G.; Bustros, Serge de; Enger, Cheryl; Katô, Hirofumi; Lansing, Mary B.

doi:10.1172/jci114065

Cited by 436 publications

(241 citation statements)

References 29 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%

“…[13][14][15][16] In the eye, all three human isoforms (TGF-b1, TGF-b2 and TGF-b3) have been found although TGF-b2 appears predominant. 17,18 TGF-b has been implicated in the pathogenesis of several ocular scarring diseases such as corneal scarring, 19 proliferative vitreoretinopathy, [20][21][22] cataract and posterior capsular scarring. [23][24][25] It is also involved in the woundhealing response following ocular surgery.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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%

Section: Introductionmentioning

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

View full text Add to dashboard Cite

show abstract

“…TGF-b is secreted in a latent form from which the mature form is released from the latency-associated peptide by proteolytic cleavage and other unknown mechanisms [9,10]. The roles of TGF-b in ocular pathophysiology and in immunoregulation are well documented [11][12][13]. Elevated expression of TGF-b in vitreous, retina and retinal pigment epithelium (RPE) has been correlated closely with retinal fibrosis and choroidal neovascularization [11].…”

Section: Introductionmentioning

confidence: 99%

“…The roles of TGF-b in ocular pathophysiology and in immunoregulation are well documented [11][12][13]. Elevated expression of TGF-b in vitreous, retina and retinal pigment epithelium (RPE) has been correlated closely with retinal fibrosis and choroidal neovascularization [11]. On the other hand, TGF-b levels in ocular fluids have been shown to be lower in uveitis patients [13].…”

Section: Introductionmentioning

confidence: 99%

Transforming growth factor-β expression in human retinal pigment epithelial cells is enhanced by Toxoplasma gondii: a possible role in the immunopathogenesis of retinochoroiditis

Nagineni

Detrick

Hooks

2002

Clinical and Experimental Immunology

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SUMMARYRetinochoroiditis caused by Toxoplasma gondii infection results in inflammation and necrosis of the retina. We have used human retinal pigment epithelial cultures (HRPE) as an in vitro model to investigate the role of TGF-b in T. gondii-induced retinochoroiditis. RT-PCR analyses showed enhanced steady state levels of TGF-b1 and TGF-b2 mRNA in T. gondii-infected HRPE. Uninfected HRPE secrete TGF-b1 in a latent form while 10-30% of the secreted TGF-b2 was in the active form. T. gondii infection induced a significant increase (P < 0·01) in total TGF-b1 and TGF-b2 secretion by HRPE. In addition, soluble extracts of T. gondii (ST) stimulated secretion of both TGF-b1 and TGF-b2 significantly (P < 0·01). Interestingly, T. gondii infection as well as ST of the parasites completely inhibited secretion of the active form of TGF-b2. Studies evaluating the effect of TGF-b on T. gondii replication in HRPE revealed that TGF-b enhanced parasite replication. The interactions between host retinal cells and T. gondii may play an active role in the pathogenesis of retinochoroiditis.

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“…This finding is in agreement with previous studies 3,39 although the difference in protein level between the PVR and non-PVR groups in this study is smaller. Connor et al 39 …”

Section: Preoperative Risk Factorsmentioning

confidence: 99%

Simple retinal detachments: identifying the at-risk case

Asaria

Gregor

2002

Eye

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The success rate of retinal reattachment surgery has now reached over 90%. The major cause of failure is attributable to the development of proliferative vitreoretinopathy (PVR). It is a complex process comprised of events that are similar to those of the wound healing response with inflammation, migration and proliferation of a variety of cells. These membranes can exert traction and reopen previously closed retinal breaks, create new breaks, and distort or obscure the macula.In the early part of this century the success rate of retinal reattachment surgery was virtually nil and it was not until a better understanding of the pathophysiology of retinal detachment was gained that the success rate improved. It was Gonin who emphasised the relationship between vitreous detachment and traction resulting in retinal tears that led to treatment aimed at closing retinal breaks.To increase even further the final success rate in the treatment of 'simple retinal detachments' a better understanding of the risk factors for PVR is needed in patients presenting with acute retinal detachments. Such risk factors can be broadly divided under the headings of preoperative risk factors, best surgical management and possibly adjuvant therapy.

show abstract

Correlation of fibrosis and transforming growth factor-beta type 2 levels in the eye.

Cited by 436 publications

References 29 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

Transforming growth factor-β expression in human retinal pigment epithelial cells is enhanced by Toxoplasma gondii: a possible role in the immunopathogenesis of retinochoroiditis

Simple retinal detachments: identifying the at-risk case

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