Sustained release of cis-hydroxyproline in the treatment of experimental proliferative vitreoretinopathy in rabbits

Abstract

Purpose. To evaluate the efficacy of sustained-release cis-4-hydroxyproline (CHP), a proline analog that inhibits collagen secretion, on experimental proliferative vitreoretinopathy (PVR) in rabbits.

Methods. To demonstrate the sustained release of CHP we developed scleral implants weighing 8.5 mg made of a homogeneous mixture of poly(D,L-lactide-co-glycolide) (PLGA) and various doses of CHP. The CHP release profiles were evaluated by high-performance liquid chromatography in vitro. Scleral implants loaded with 20% and 15% of CHP and made from PLGA (copolymer ratios 65/35 and 50/50; mean molecular weights 103,000 and 93,000, respectively) were used to treat experimental PVR and the efficacy was studied. In treated eyes, two PLGA 65/35 implants (n=7), PLGA 50/50 implants (n=6), or a PLGA 65/35 and a PLGA 50/50 implant (n=9) were inserted at the pars plana, followed by PVR induction with autologous fibroblasts. Control eyes (n=18) received two implants without CHP. Ocular tissue toxicity was evaluated histologically.

Results. In vitro release studies demonstrated a triphasic release pattern. The PLGA 65/35 and PLGA 50/50 implants released CHP over 4 and 7 weeks, respectively. The PLGA 65/35 implants decreased the incidence of retinal detachment from 89% (in controls) to 57% on day 28. When both PLGA 65/35 and PLGA 50/50 implants were used, the inhibitory effect was synergistically enhanced (p=0.0034), while implantation with only PLGA 50/50 implants had no significant effect on PVR. No toxic reactions were observed.

Conclusion. These results suggest that the biodegradable polymeric implants containing CHP represent a potential treatment for PVR.