Mechanisms accounting for the development of proliferative vitreoretinopathy (PVR) in patients with rhegmatogenous retinal detachment remain poorly understood. In a previous study, we found the presence of various growth factors in preretinal membranes that were surgically removed from patients with PVR. The present immunohistological study was undertaken in intravitreal and subretinal fluid cells from patients suffering from PVR in various stages of development, in order to seek the presence of 4 growth-promoting factors for retinal pigment epithelial cells: acidic fibroblast growth factor (FGF), epidermal growth factor (EGF), insulin-like growth factor type I (IGF-I) and transforming growth factor-beta (TGF-β). Results were quite similar in vitreous and subretinal fluid. Acidic FGF was found in all vitreous and subretinal specimens, in 30-100% of the examined cells. Immunoreactivity for EGF could be found in 53% of intravitreal cells and 69% of subretinal fluid cells. Positive cells were seen in all vitreous specimens and in all but 1 of the subretinal fluid specimens. IGF-I-containing cells were present in 13 of 15 vitreous specimens and in 18 of 20 subretinal fluid samples (mean percentages of reactivity in positive specimens 70% and 78%, respectively). In contrast, TGF-β1 reactivity was found in only 8 of 15 vitreous specimens and in 11 of 20 subretinal samples. Mean percentages of reactive cells were 30% and 50%, respectively. These results suggest that several growth factors could be involved in the proliferation and migration of retinal pigment epithelial cells during the course of PVR. Their respective role and whether they act solely or synergistically are, however, some of the numerous questions that remain to be investigated.

After the debridement of the entire corneal epithelium of the rabbit eye, epithelial cells of conjunctival origin cover the denuded corneal surface. Under such experimental conditions, the rate of wound healing is considerably delayed and total regeneration is completed within 15 to 20 days, allowing evaluation of various drugs, such as the Fibroblast Growth Factor. Both acidic and basic FGF were administered topically on totally de-epithelialized rabbit eye, at three different concentrations of 1.5 and 10 Stimulation Units/50 microliters, 3 times per day. A dose-response effect was observed and in each case, acidic FGF was found to be much more potent than bFGF in increasing the rate of wound healing of the cornea. These results are correlated with a new purification procedure, avoiding acid treatment of the tissue extract. The systemic diffusion of FGF allows the contralateral eye cells to be also stimulated for mitosis and migration and to heal faster than the control eyes.

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Soluble dextran polymer derivatives (CMDBSs) are originally synthesized as heparin-like plasma substitutes. Some of them mimic heparin in its interactions and stabilize, protect and facilitate actions of heparin binding growth factors. The wound healing activity of one specific CMDBS was studied in a model of corneal ulcer on the rabbit eye and compared with the activity of basic fibroblast growth factors (bFGF) added alone or in association with CMDBS. Total reepithelialization was observed with bFGF + CMDBS, bFGF alone and CMDBS alone after, respectively, 3.8 ± 0.78, 4.3 ± 0.67 and 4.4 ± 0.51 days. All treatments were efficient if compared with eyes treated with saline (p < 0.0001). The grade of significance of the applied treatments was as follows: bFGF + CMDBS > bFGF > CMDBS > saline. Our study pinpoints that some specific CMDBS are as potent agents as bFGF for corneal ulcer healing, and can therefore be proposed for therapeutic use.

The development and extension of fibrovascular or fibroglial membranes onto the retinal surface are a major cause of visual loss in diabetic patients with proliferative retinopathy and in patients suffering from retinal detachment with proliferative vitreoretinopathy. The pathogenesis of these proliferative diseases, however, remain poorly understood and the nature of growth-promoting mediators implicated in these phenomena has not been determined yet. Using indirect immunofluorescence procedures, three different growth factors known to be mitogenic for various cell components of preretinal membranes, acidic fibroblast growth factor, epidermal growth factor and insulin-like growth factor type I, were sought in 14 specimens of preretinal proliferative tissues. Similar results were obtained in diabetic preretinal membranes and tissues from patients with proliferative vitreoretinopathy. The three different growth factors were found diffusely in the connective stroma and around new blood vessels within the vascular walls. Some fibroblast-like and pigment epithelial-derived cells more markedly reacted with anti-growth factor antibodies. These results provide indications on the eventual involvement of three potent growth factors in intraocular proliferative diseases, but whether or not these mediators play an active role in the development of preretinal membranes remains to be determined.