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


CONCLUSIONS
These results suggest that the biodegradable polymeric implants containing CHP represent a potential treatment for PVR.
Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Kyoto, Japan.
Tsutomu
T
Yasukawa
Hideya
H
Kimura
Yasuhiko
Y
Tabata
Hideki
H
Miyamoto
Yoshihito
Y
Honda
Yuichiro
Y
Ogura
D020341:Absorbable Implants; D000818:Animals; D001672:Biocompatible Materials; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004337:Drug Carriers; D005347:Fibroblasts / Q000187:drug effects; D006909:Hydroxyproline / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019344:Lactic Acid; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011817:Rabbits; D012590:Sclera / Q000601:surgery; D018630:Vitreoretinopathy, Proliferative / Q000188:drug therapy* / Q000473:pathology
D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006909:Hydroxyproline