Correlation of fibrosis and transforming growth factor-beta type 2 levels in the eye.
Approximately 1 out of every 10 eyes undergoing surgery for retinal detachment develops excessive intraocular fibrosis that can lead to traction retinal detachment and ultimate blindness. This disease process has been termed proliferative vitreoretinopathy (PVR). The ability to monitor and grade this fibrotic response accurately within the eye as well as the ability to aspirate vitreous cavity fluid bathing the fibrotic tissue makes this an ideal setting in which to investigate the development of fibrosis. Although laboratory studies have recently shown that transforming growth factor-beta (TGF-beta) can enhance fibrosis, little clinical evidence is yet available correlating the level of this or other growth factors with the degree of fibrosis in a clinical setting. We have found that vitreous aspirates from eyes with intraocular fibrosis associated with PVR have more than three times the amount of TGF-beta (1,200 +/- 300 pM [SEM]) found in eyes with uncomplicated retinal detachments without intraocular fibrosis (360 +/- 91 pM [SEM]). Using an in vitro assay, 84-100% of the TGF-beta activity could be blocked with specific antibodies against TGF-beta 2, whereas only 10-21% could be blocked by specific antibodies against TGF-beta 1. TGF-beta 1 was used in an animal model of traction retinal detachment. Since beta 1 and beta 2 have essentially identical biologic effects and only human beta 1 was available in quantities required, beta 1 was chosen for these in vivo studies. The injection of TGF-beta1 plus fibronectin (FN) but not TGF-beta1 alone into the vitreous cavity of rabbits resulted in the increased formation of intraocular fibrosis and traction retinal detachments as compared to control eyes. In previous studies, intravitreal FN levels were also found to be elevated in eyes with intraocular fibrosis.
Connor
T B
TB
Center for Vitreoretinal Research, Wilmer Ophthalmological Institute, Baltimore, Maryland 21205, USA.
Roberts
A B
AB
Sporn
M B
MB
Danielpour
D
D
Dart
L L
LL
Michels
R G
RG
de Bustros
S
S
Enger
C
C
Kato
H
H
Lansing
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000906:Antibodies / Q000502:physiology; D001667:Binding, Competitive; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D012163:Retinal Detachment / Q000378:metabolism / Q000473:pathology*; D015291:Transforming Growth Factors / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D014822:Vitreous Body / Q000378:metabolism / Q000473:pathology*
D000906:Antibodies; D006131:Growth Inhibitors; D015291:Transforming Growth Factors