title: Quantitative evaluation for blood-retinal barrier breakdown in experimental retinal vein occlusion produced by photodynamic thrombosis using a new photosensitizer.
abstract: Purpose. To establish a rat model of retinal vein occlusion (RVO), we applied photodynamic thrombosis using a new photosensitizer. By measuring the breakdown of the blood-retinal barrier (BRB), we evaluated the model quantitatively. We also investigated how hypertension and retinal pigment epithelium (RPE) influence the breakdown of BRB after RVO. Methods. We modified a slit lamp biomicroscope for photodynamic thrombosis. The light source was changed from white light to argon laser, which made it possible to perform fluorescein angiography (FAG) simultaneously during photodynamic thrombosis. We irradiated with a continuous diode laser to occlude three retinal veins in a rat after PAD-S31 injection. The breakdown of BRB was quantitated by measuring extravasated Evans blue dye in albino and pigmented rats. We compared hypertensive rats (SHR) to normotensive rats (WKY) and sodium iodate-treated rats to normal rats. Results. High photosensitivity of PAD-S31 made it possible to occlude any retinal veins within 120 seconds at a low dose of 10 mg/kg without retinal thermal burn at the occlusion site. Simultaneous FAG enabled us to observe the formation of thrombus during diode laser irradiation. Our measured value of intraretinal Evans blue correlated with the range of serous retinal detachment. Both albino and pigmented rats demonstrated stable and constant values of Evans blue. SHR recovered from the breakdown of BRB after venous occlusion more slowly than WKY. Sodium iodate-treated rats had smaller breakdowns of BRB and recovered earlier than normal rats. Conclusions. In this study, we established the stable and constant rat model of RVO efficiently by using a new photosensitizer. Our simultaneous FAG method was considered to have an advantage of several potential clinical applications. Our rat model of RVO allows us to study factors associated with the recovery from damage by RVO.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ieki
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nishiwaki
authors.forename: Shinji
authors.initials: S
authors.lastname: Miura
authors.forename: Yuya
authors.initials: Y
authors.lastname: Hirata
authors.forename: Isao
authors.initials: I
authors.lastname: Sakata
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nonaka
authors.forename: Junichi
authors.initials: J
authors.lastname: Kiryu
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Honda
mesh_terms: D000818:Animals; D001813:Blood-Retinal Barrier; D019559:Capillary Leak Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology*; D016022:Case-Control Studies; D004195:Disease Models, Animal; D005069:Evaluation Studies as Topic; D005070:Evans Blue / Q000378:metabolism; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D006973:Hypertension / Q000150:complications; D007452:Iodates / Q000627:therapeutic use; D008297:Male; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000378:metabolism / Q000494:pharmacology*; D010857:Pigment Epithelium of Eye / Q000187:drug effects; D011166:Porphyrins / Q000378:metabolism / Q000494:pharmacology; D011859:Radiography; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012163:Retinal Detachment / Q000175:diagnosis; D012169:Retinal Vein / Q000000981:diagnostic imaging; D012170:Retinal Vein Occlusion / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology*; D013045:Species Specificity; D013927:Thrombosis / Q000209:etiology / Q000473:pathology*; D013997:Time Factors
chemical_list: C446480:13,17-bis(1-carboxypropionyl)carbamoylethyl-3-ethenyl-8-ethoxyiminoethylidene-7-hydroxy-2,7,12,18-tetramethyl porphyrin; D007452:Iodates; D017319:Photosensitizing Agents; D011166:Porphyrins; D005070:Evans Blue; C032285:sodium iodate