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Article
December 1995

Pathologic Human Vitreous Promotes Contraction by FibroblastsImplications for Proliferative Vitreoretinopathy

Author Affiliations

From the Department of Ophthalmology, University of Alabama at Birmingham (Drs Hardwick and Guidry), the Helen Keller Eye Research Institute, Birmingham (Drs Morris and Witherspoon), the Retina Consultants of Alabama, Birmingham (Drs White and Feist); and the Institute of Bioscience and Technology, Texas A&M University, Houston (Ms McFarland).

Arch Ophthalmol. 1995;113(12):1545-1553. doi:10.1001/archopht.1995.01100120075013
Abstract

Objectives:  To establish and quantify the presence of contraction-stimulating activity in pathologic vitreous and correlate this activity with clinical presentation and outcome, especially with proliferative vitreoretinopathy.

Methods:  Contraction-stimulating activity of vitreous collected during surgery was quantified with a tissue culture assay using fibroblasts as target cells. The activity of each sample was correlated with patient history, clinical presentation, risk factors, proliferative disease, and postoperative proliferation.

Results:  Pathologic vitreous contained measurable quantities of contraction-stimulating activity and stimulated contraction in vitro, with elevated activities in samples from patients with proliferative vitreoretinopathy, epimacular proliferation, retinal detachment, retinal defects, pigmented cells in the vitreous, hemorrhage, or uveitis. Patients with postoperative proliferation had significantly elevated mean activities.

Conclusions:  Levels of contraction-stimulating activity in pathologic vitreous correlate with some risk factors for the development of proliferative vitreoretinopathy and may ultimately be useful in the assessment of disease severity and the prediction of postoperative proliferation.

References
1.
Hanneken A, Michels R.  Surgical treatment of PVR . In: Freeman H, Toletino F, eds. Proliferative Vitreoretinopathy (PVR) . New York, NY: Springer-Verlag NY Inc; 1988:60-69.
2.
Baudouin C, Fredj-Reygrobellet D, Brignole F, Negre F, Lapalus P, Gastaud P.  Growth factors in vitreous and subretinal fluid cells from patients with proliferative vitreoretinopathy . Ophthalmic Res . 1993;25:52-59.Article
3.
McCuen B, Landers M, Machemer R.  The use of silicone oil following failed vitrectomy for retinal detachment with advanced proliferative vitreoretinopathy . Ophthalmology . 1985;92:1029-1033.Article
4.
Machemer R.  Proliferative vitreoretinopathy (PVR): a personal account of its pathogenesis and treatment . Invest Ophthalmol Vis Sci . 1988;29:1771-1783.
5.
Weller M, Wiedemann P, Heimann K.  Proliferative vitreoretinopathy: is it anything more than wound healing at the wrong place? Int Ophthalmol . 1990;14:105-117.Article
6.
Cowley M, Conway B, Campochiaro P, Kaiser D, Gaskin H.  Clinical risk factors for proliferative vitreoretinopathy . Arch Ophthalmol . 1989;107:1147-1151.Article
7.
Hutton W, Fuller D, Snyder W.  Silicone oil for management of PVR: comparison of six-month and two-year results . In: Freeman H, Toletino F, eds. Proliferative Vitreoretinopathy (PVR) . New York, NY: Springer-Verlag NY Inc; 1988:166-168.
8.
Lewis H, Aaberg T, Abrams G.  Causes of failure after initial vitreoretinal surgery for severe proliferative vitreoretinopathy . Am J Ophthalmol . 1991;111:8-14.
9.
Machemer R, Laqua H.  Pigment epithelium proliferation in retinal detachment (massive periretinal proliferation) . Am J Ophthalmol . 1975;80:1-23.
10.
Weller M, Heimann K, Wiedemann P.  The pathogenesis of vitreoretinal proliferation and traction: a working hypothesis . Med Hypotheses . 1990;31:157-159.Article
11.
Cousins S, Rubsamen P.  Comparison of flow cytometry with the surgeon regarding ability to predict the ultimate success of surgery for proliferative vitreoretinopathy . Arch Ophthalmol . 1994;112:1554-1560.Article
12.
Wiedemann P, Weller M. The pathophysiology of proliferative vitreoretinopathy . Acta Ophthalmologica (Copenh) . 1988;189:4-15.
13.
Bell E, Ivarsson B, Merril C.  Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro . Proc Natl Acad Sci U S A . 1979;76:1274-1278.Article
14.
Steinberg B, Smith K, Colozzo M, Pollack R.  Establishment and transformation diminish the ability of fibroblasts to contract a native collagen gel . J Cell Biol . 1980;87:304-308.Article
15.
Guidry C, Grinnell F. Contraction of hydrated collagen gels by fibroblasts: evidence for two mechanisms through which fibrils are stabilized . Coll Related Res . 1986;6:515-529.Article
16.
Guidry C, Grinnell F.  Studies on the mechanism of hydrated collagen gel reorganization by human skin fibroblasts . J Cell Sci . 1985;79:67-81.
17.
Gullberg D, Tingstrom A, Thuresson A-C, et al.  Beta-1 integrin-mediated collagen gel contraction is stimulated by PDGF . Exp Cell Res . 1990;186:264-272.Article
18.
Klein C, Dressel D, Steinmayer T, et al.  Integrin alpha 2 beta 1 is upregulated in fibroblasts and highly aggressive melanoma cells in three-dimensional collagen lattices and mediates the reorganization of collagen I fibrils . J Cell Biol . 1991;115:1427-1436.Article
19.
Schiro J, Chan B, Roswit W, et al.  Integrin α2 β1 (VLA-2) mediates reorganization and contraction of collagen matrices by human cells . Cell . 1991;67:403-410.Article
20.
Kupper T, Ferguson T.  A potential pathophysiologic role for α2 β1 integrin in human eye diseases involving vitreoretinal traction . FASEB J . 1993;7:1401-1406.
21.
Hunt R, Pakalnis V, Choudhury P, Black P.  Cytokines and serum cause α2 β1 integrin-mediated contraction of collagen gels by cultured retinal pigment epithelial cells . Invest Ophthalmol Vis Sci . 1994;35:955-963.
22.
Glaser B, Cardin A, Biscoe B.  Proliferative vitreoretinopathy: the mechanism of development of vitreoretinal detachment . Ophthalmology . 1987;94:327-332.Article
23.
Yamakawa R, Sorgente N, Ryan S.  Investigations on contractile properties of retinal pigment epithelial cells . Ophthalmologica . 1989;199:165-172.Article
24.
Raymond M, Thompson J.  RPE-mediated collagen gel contraction: inhibition by colchicine and stimulation by TGF-α . Invest Ophthalmol Vis Sci . 1990;31:1070-1086.
25.
Guidry C, McFarland R, Morris R, Witherspoon C, Hook M.  Collagen gel contraction by cells associated with proliferative vitreoretinopathy . Invest Ophthalmol Vis Sci . 1992;33:85-91.
26.
Mazure A, Grierson I.  In vitro studies of the contractility of cell types involved in proliferative vitreoretinopathy . Invest Ophthalmol Vis Sci . 1992;33:3407-3416.
27.
Grisanti S, Guidry C.  Transdifferentiation of retinal pigment epithelial cells from epithelial to mesenchymal phenotype . Invest Ophthalmol Vis Sci . 1995;35:391-405.
28.
Finesmith T, Broadley K, Davidson J.  Fibroblasts from wounds of different stages of repair vary in their ability to contract a collagen gel in response to growth factors . J Cell Physiol . 1990;144:99-107.Article
29.
Guidry C, Hardwick C.  Extracellular matrix contraction by choroidal fibroblasts: Inhibition by staurosporine . Invest Ophthalmol Vis Sci . 1994;35:50-508.
30.
de Juan E, Dickson J, Hatchell D.  Interaction of retinal glial cells with collagen matrices: implications for pathogenesis of cell-mediated traction . Graefes Arch Clin Exp Ophthalmol . 1989;227:494-498.Article
31.
Guidry C, Hohn S, Hook M.  Endothelial cells secrete a factor that promotes fibroblast contraction of hydrated collagen gels . J Cell Biol . 1990;110:519-528.Article
32.
Montesano R. Orci L.  Transforming growth factor β stimulates collagen-matrix contraction by fibroblasts: implication for wound healing . Proc Natl Acad Sci US A . 1988;85:4894-4897.Article
33.
Ura H, Obara T, Yokota K, Shibata Y, Okamura K, Namiki M.  Effects of transforming growth factor-β released from gastric carcinoma cells on the contraction of collagen-matrix gels containing fibroblasts . Cancer Res . 1991;51:3550-3554.
34.
Pena R, Jerdan J, Glaser B.  Effects of TGF-β and TGF-β neutralizing antibodies on fibroblast-induced collagen gel contraction: implications for proliferative vitreoretinopathy . Invest Ophthalmol Vis Sci . 1994;35:2804-2808.
35.
Anderson S, Reben Z, Fuller G.  Cell-mediated contraction of collagen lattices in serum-free medium: effect of serum and nonserum factors . In Vitro Cell Dev Biol . 1990;26:61-66.Article
36.
Clark R, Folkvord J, Hart C, Murray M, McPherson J.  Platelet isoforms of platelet-derived growth factor stimulate fibroblasts to contract collagen matrices . J Clin Invest . 1989;84:1036-1040.Article
37.
Guidry C, Hook M.  Endothelins produced by endothelial cells promote collagen gel contraction by fibroblasts . J Cell Biol . 1991;115:873-880.Article
38.
Wiedemann P.  Growth factors in retinal diseases: proliferative vitreoretinopathy. proliferative diabetic retinopathy, and retinal degeneration . Surv Ophthalmol . 1992;36:373-384.Article
39.
Connor T, Roberts A, Sporn M, et al.  Correlation of fibrosis and transforming growth factor β type 2 levels in the eye . J Clin Invest . 1989;83:1661-1666.Article
40.
Chakravarthy U, Douglas A, Bailie J, McKibben B, Archer D.  Immunoreactive endothelin distribution in ocular tissues . Invest Ophthalmol Vis Sci . 1994;35:2448-2454.
41.
Liggett P, Deuel T, Freeman W, Rao N, Ryan S.  Platelet-derived growth factor in choroidal melanoma . Invest Ophthalmol Vis Sci . 1986;27:132. Abstract.
42.
Machemer, R, Aaberg T, Freeman H, et al.  An updated classification of retinal detachment with proliferative vitreoretinopathy . Am J Ophthalmol . 1991;112:159-165.
43.
Bonnet M.  Clinical factors predisposing to massive proliferative vitreoretinopathy in rhegmatogenous retinal detachment . Ophthalmologica . 1984;188:148-152.Article
44.
Bonnet M.  The development of severe proliferative vitreoretinopathy after retinal detachment surgery: grade B, a determining risk factor . Graefes Arch Clin Exp Ophthalmol . 1988;226:201-205.Article
45.
Brown B, Hollander M. Statistics: A Biomedical Introduction . New York, NY: John Wiley & Sons; 1977.
46.
Lewis H. Vitreoretinal surgery and silicone oil injection for severe penetrating ocular trauma in children. Presented at the Third International Symposium on Ocular Trauma; March 10-14, 1994; Cancun, Mexico.
47.
Guidry C.  Extracellular matrix contraction by fibroblasts: peptide promoters and second messengers . Cancer Metastasis Rev . 1992;11:45-54.Article
48.
Guidry C.  Fibroblast contraction of collagen gels requires activation of protein kinase C . J Cell Physiol . 1993;155:358-367.Article
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