title: Pirfenidone inhibits post-traumatic proliferative vitreoretinopathy.
abstract: PurposeThe 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 methodsPenetrating 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 (TGFβ), alpha smooth muscle actin (αSMA), 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.ResultsClinical 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, αSMA, and TGFβ 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.ConclusionThis 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.
authors.affiliation: Department of Veterinary Surgery &Radiology, West Bengal University of Animal &Fishery Sciences, Kolkata, India.
authors.forename: B N M K
authors.initials: BNMK
authors.lastname: Khanum
authors.affiliation: CSIR-Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: R
authors.initials: R
authors.lastname: Guha
authors.affiliation: CSIR-Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: V P
authors.initials: VP
authors.lastname: Sur
authors.affiliation: CSIR-Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: S
authors.initials: S
authors.lastname: Nandi
authors.affiliation: Disha Eye Hospitals, Kolkata, India.
authors.forename: S K
authors.initials: SK
authors.lastname: Basak
authors.affiliation: CSIR-Indian Institute of Chemical Biology, Kolkata, India.
authors.forename: A
authors.initials: A
authors.lastname: Konar
authors.affiliation: Department of Veterinary Surgery &Radiology, West Bengal University of Animal &Fishery Sciences, Kolkata, India.
authors.forename: S
authors.initials: S
authors.lastname: Hazra
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D024042:Collagen Type I / Q000378:metabolism; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D004596:Electroretinography; D015807:Eye Injuries, Penetrating / Q000188:drug therapy* / Q000209:etiology; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation / Q000502:physiology; D058449:Intravitreal Injections; D011728:Pyridones / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000293:injuries*; D018630:Vitreoretinopathy, Proliferative / Q000188:drug therapy* / Q000209:etiology; D014822:Vitreous Body / Q000378:metabolism
chemical_list: D000199:Actins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D024042:Collagen Type I; D016207:Cytokines; D011728:Pyridones; C093844:pirfenidone