Basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGF-beta) act as stop and go signals to modulate postnatal ocular growth in the chick.
Occlusion of the eye (form deprivation) during post-natal development leads to ocular enlargement and myopia. The chick model of form deprivation myopia (FDM) has been used to identify candidate factors that underly the control of ocular growth. The major biochemical change associated with eye enlargement is an increase in scleral cartilage proteoglycan production (Rada et al., 1991) which is reduced in recovering eyes. Thus increasing evidence suggests that in the chicken eye, two different signals are involved, one for stop (occluder off) and one for go (occluder on). Because transforming growth factor-beta (TGF-beta) and basic fibroblast growth factor (bFGF) are known to act in a push-pull manner in regulating extracellular matrix, their possible roles in FDM were tested. Chicks were occluded monocularly for 8 days, after which axial dimensions were assessed using A-scan ultrasonography, and refractive errors using streak retinoscopy. Under light halothane anesthesia, the control group received daily vehicle injections into both eyes whereas the experimental groups were treated with growth factors in the occluded eye and vehicle in the unoccluded eye. It was shown that: (1) bFGF reduced FDM in a dose-dependent manner, with a 50% effective dose (ED50) of 1.05 and 1.67 ng for subconjunctival and intravitreal delivery, respectively. Both axial eye length and refraction were similarly affected. The effects were mainly confined to a decrease in vitreous chamber depth. The anterior chamber was less deep but only after intravitreal injections, whereas lens thickness was not affected at all. At maximum effect, after subconjunctival applications the bFGF-treated occluded eyes were only 0.09 +/- 0.16 mm longer than controls, which corresponded to a refractive error of -0.67 +/- 0.82 diopters (D), whereas after intravitreal applications the difference in axial eye length was -0.07 +/- 0.19 mm, corresponding to -0.3 +/- 0.52 D. (2) This effect could be mimicked by aFGF, but with a potency approximately 160 times less than that of bFGF. The aFGF rescue effect could only be demonstrated for subconjunctival delivery; high intravitreal doses (> or = 300 ng per injection) induced retinal detachment and photoreceptor degeneration, while doses of aFGF close to the ED50 for bFGF (3 ng per injection) were completely ineffective. (3) TGF-beta 1 was not found to induce myopia in unoccluded eyes, or to increase myopia in occluded eyes. It was, however, a potent inhibitor of the bFGF rescue effect, if administered together with bFGF in the subconjunctival space.(ABSTRACT TRUNCATED AT 400 WORDS)
Rohrer
B
B
Lions' Sight Centre, University of Calgary, Faculty of Medicine, Alberta, Canada.
Stell
W K
WK
D000818:Animals; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D005123:Eye / Q000187:drug effects* / Q000254:growth & development*; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D009216:Myopia / Q000209:etiology / Q000503:physiopathology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012683:Sensory Deprivation; D016212:Transforming Growth Factor beta / Q000494:pharmacology* / Q000502:physiology
D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2