EVALUATION OF ANTIPROLIFERATIVE EFFECTS OF THE SOMATOSTATIN ANALOG SOMATULINE IN A RABBIT MODEL OF TRACTION RETINAL-DETACHMENT

As growth hormone (GH) and insulin-like growth factor type I (IGF-I) have been suggested to be involved in the development of some proliferative ocular disorders, we investigated the eventual antiproliferative properties of a long acting somatostatin analogue, somatuline or BIM23014 (IPSEN Biotech, France), in an original model of experimental proliferative vitreoretinopathy. Two studies were separately done to investigate respective effects of subcutaneously- and intravitreally administered somatuline. Injections of 10(7) human platelets freshly prepared from a unique normal donor were injected into the vitreous, cavity of pigmented rabbits. The first experiment consisted of evaluating vitreoretinal proliferation in 17 eyes from rabbits receiving subcutaneous injections of 25 mu g/kg of BIM23014, given twice a day, from the day after injection for one month. A group of 14 eyes served as non treated controls. The second experiment was conducted in 33 eyes: 10 received intravitreally 1 mu g of somatuline given once a week for one month, 10 eyes similarly received 5 mu g/week of somatuline, the remaining 13 eyes serving as controls with intravitreal injections of sterile saline. All animals were examined ophthalmoscopically twice a week for one month in a masked manner, and sacrificed at the end of the experiment for histological and immunohistological analyses. In all but two eyes from the subcutaneously treated group, intravitreal and preretinal membranes formed, five to eight days after platelet injection. Intravitreal proliferation progressively increased, resulting in various degrees of vitreoretinal retraction and retinal detachment. Finally, comparison between eyes from animals receiving subcutaneous BIM23014 and non treated control eyes showed significantly fewer retinal detachments in the treated ones (7/17 vs 11/14, p < 0.05) and significantly lower proliferation scores at the end of the experiment (3.79 +/- 1.25 vs 2.24 +/- 1.78, p = 0.01). In contrast, comparisons between intravitreally treated and untreated control eyes showed no difference, nor protective effect of intraocular somatuline. Histological examination revealed similarly in all groups intravitreal lymphocytes and proliferation of keratin- or vimentin-positive cells forming various patterns of preretinal membranes and retinal retraction. BIM23014 thus showed a significant reduction of vitreoretinal proliferation, but only when given systemically. These results suggest a therapeutic interest in proliferative retinopathies, but additional studies will be necessary to better understand the role of GH, IGF-I and somatostatin in these disorders.