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) h ave been suggested to be involved in the development of some prolifera tive ocular disorders, we investigated the eventual antiproliferative properties of a long acting somatostatin analogue, somatuline or BIM23 014 (IPSEN Biotech, France), in an original model of experimental prol iferative vitreoretinopathy. Two studies were separately done to inves tigate respective effects of subcutaneously- and intravitreally admini stered somatuline. Injections of 10(7) human platelets freshly prepare d from a unique normal donor were injected into the vitreous, cavity o f pigmented rabbits. The first experiment consisted of evaluating vitr eoretinal 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 treat ed controls. The second experiment was conducted in 33 eyes: 10 receiv ed 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 sa line. All animals were examined ophthalmoscopically twice a week for o ne month in a masked manner, and sacrificed at the end of the experime nt for histological and immunohistological analyses. In all but two ey es from the subcutaneously treated group, intravitreal and preretinal membranes formed, five to eight days after platelet injection. Intravi treal proliferation progressively increased, resulting in various degr ees of vitreoretinal retraction and retinal detachment. Finally, compa rison between eyes from animals receiving subcutaneous BIM23014 and no n 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 intravitreall y treated and untreated control eyes showed no difference, nor protect ive effect of intraocular somatuline. Histological examination reveale d similarly in all groups intravitreal lymphocytes and proliferation o f keratin- or vimentin-positive cells forming various patterns of prer etinal membranes and retinal retraction. BIM23014 thus showed a signif icant reduction of vitreoretinal proliferation, but only when given sy stemically. These results suggest a therapeutic interest in proliferat ive retinopathies, but additional studies will be necessary to better understand the role of GH, IGF-I and somatostatin in these disorders.