Pirfenidone inhibits post-traumatic proliferative vitreoretinopathy

• Published in: Eye (London) 2017-09, Vol.31 (9), p.1317-1328
• Main Authors: Khanum, B N M K, Guha, R, Sur, V P, Nandi, S, Basak, S K, Konar, A, Hazra, S
• Format: Article
• Language: English
• Subjects: 13/21; 13/51; 38/77; 631/61; 692/420; Actin; Actins - metabolism; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Chromatography, High Pressure Liquid; Collagen; Collagen Type I - metabolism; Cytokines; Cytokines - genetics; Disease Models, Animal; Electroretinography; Eye; Eye Injuries, Penetrating - drug therapy; Eye Injuries, Penetrating - etiology; Fluorescent Antibody Technique, Indirect; Gene expression; Gene Expression Regulation - physiology; High-performance liquid chromatography; Histology; Histopathology; Immunohistochemistry; Injection; Intravitreal Injections; Laboratory Medicine; Laboratory Study; Medicine; Medicine & Public Health; Ophthalmology; Pharmaceutical Sciences/Technology; Polymerase chain reaction; Pyridones - pharmacokinetics; Pyridones - therapeutic use; Rabbits; Real-Time Polymerase Chain Reaction; Retina; Retina - injuries; Smooth muscle; Surgery; Surgical Oncology; Transforming growth factor-b; Trauma; Vitreoretinopathy, Proliferative - drug therapy; Vitreoretinopathy, Proliferative - etiology; Vitreous Body - metabolism
• ISSN: 0950-222X; 1476-5454
• DOI: 10.1038/eye.2017.21

Purpose The purpose of the study was to evaluate the efficacy and safety of intravitreal pirfenidone for inhibition of proliferative vitreoretinopathy (PVR) in a model of penetrating ocular injury. Patients and methods Penetrating trauma was induced on the retina of rabbit and treated either with 0.1 ml of phosphate-buffered saline (PBS) or 0.1 ml of 0.5% pirfenidone, and development of PVR was evaluated clinically and graded after 1 month. Histopathology and immunohistochemistry with transforming growth factor beta (TGF β ), alpha smooth muscle actin ( α SMA), and collagen-1 were performed to assess the fibrotic changes. Expression of cytokines in the vitro-retinal tissues at different time points following pirfenidone and PBS injection was examined by RT-PCR. Availability of pirfenidone in the vitreous of rabbit at various time points was determined by high-performance liquid chromatography following injection of 0.1 ml of 0.5% pirfenidone. In normal rabbit eye, 0.1 ml of 0.5% pirfenidone was injected to evaluate any toxic effect. Results Clinical assessment and grading revealed prevention of PVR formation in pirfenidone-treated animals, gross histology, and histopathology confirmed the observation. Immunohistochemistry showed prevention in the expression of collagen-I, α SMA, and TGF β in the pirfenidone-treated eyes compared to the PBS-treated eyes. Pirfenidone inhibited increased gene expression of cytokines observed in control eyes. Pirfenidone could be detected up to 48 h in the vitreous of rabbit eye following single intravitreal injection. Pirfenidone did not show any adverse effect following intravitreal injection; eyes were devoid of any abnormal clinical sign, intraocular pressure, and electroretinography did not show any significant change and histology of retina remained unchanged. Conclusion This animal study shows that pirfenidone might be a potential therapy for PVR. Further clinical study will be useful to evaluate the clinical application of pirfenidone.