sodium-iodate and Retinal-Detachment

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.

Topics: Animals; Blood-Retinal Barrier; Capillary Leak Syndrome; Case-Control Studies; Disease Models, Animal; Evaluation Studies as Topic; Evans Blue; Fluorescein Angiography; Fundus Oculi; Hypertension; Iodates; Male; Photochemistry; Photosensitizing Agents; Pigment Epithelium of Eye; Porphyrins; Radiography; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Retinal Detachment; Retinal Vein; Retinal Vein Occlusion; Species Specificity; Thrombosis; Time Factors

The subretinal fluid of serous retinal detachments contains protein, but little is known about its origin and fate. The authors designed experiments to study the rate and route of albumin movement out of the subretinal space.. Experimental retinal detachments were made in Dutch rabbits by injecting Hanks' balanced salt solution containing serum levels (approximately 30 mg/ml) of fluorescein isothiocyanate (FITC) albumin into the subretinal space through a micropipette. Subretinal, vitreous, and serum fluid samples were withdrawn 0 to 4 hours later through a similar micropipette and were analyzed for osmolality, FITC albumin content (by fluorophotometry) and FITC+native albumin content (by gel electrophoresis). Sodium iodate was injected intravenously in some rabbits to damage the retinal pigment epithelium (RPE).. Albumin injected into the subretinal fluid diffused steadily into the vitreous, and its concentration decreased by approximately 5% per hour. This rate was unaffected by RPE damage. Albumin did not move into the bloodstream unless the RPE was damaged with sodium iodate, and then it crossed the RPE at approximately 25% of the rate at which it moved into the vitreous. Subretinal fluid osmolality remained within the range of 293 to 294 mOsm/kg despite protein movement and the continual absorption of fluid from the detachments.. These results show that albumin in the subretinal space diffuses readily into the vitreous, and subretinal osmolality changes are rapidly equilibrated with the vitreous. Albumin does not cross normal RPE, and it crosses iodate-damaged RPE more slowly than it crosses retina. Thus, there must be a constant supply of albumin if high subretinal concentrations are to be sustained in clinical serous detachments.

Topics: Animals; Biological Transport; Blood-Retinal Barrier; Body Fluids; Extracellular Space; Fluorescein-5-isothiocyanate; Fluorophotometry; Iodates; Osmolar Concentration; Pigment Epithelium of Eye; Rabbits; Retinal Detachment; Serum Albumin, Bovine; Vitreous Body

To investigate the rate and source of albumin entry into experimental nonrhegmatogenous detachments.. Detachments were made in Dutch rabbits by injecting Hanks' balanced salt solution into the subretinal space through a micropipette. Subretinal fluid was withdrawn 0 to 4 hours later through a similar micropipette and analyzed for osmolality and albumin content (by gel electrophoresis). Sodium iodate was injected intravenously in some rabbits to damage the retinal pigment epithelium (RPE). In some rabbits fluorescein isothiocyanate albumin (FITC-albumin) was injected intravitreally or intravenously to measure its entry into the subretinal fluid by fluorophotometry. Results from 4 to 8 eyes were averaged for each data point.. The albumin concentration and total amount of albumin in the subretinal fluid increased steadily over 4 hours in retinal detachments initially filled with Hanks' solution. Pretreating rabbits with sodium iodate injection resulted in a 50-fold increase in the rate of albumin entry, although the levels were still low relative to those of serum. Intravitreal FITC-albumin entered the subretinal fluid at a rate independent of sodium iodate damage, but intravenous FITC-albumin only entered the subretinal space after RPE damage. Subretinal fluid osmolality remained within the range of 291 to 294 mOsm/kg, irrespective of sodium iodate damage or differences in the rate of fluid absorption.. These results indicate that albumin can diffuse into the rabbit subretinal space from both vitreous and bloodstream, although entry from serum requires damage to the RPE. Subretinal fluid appears to be transported actively (control eyes) or passively (iodate-damaged eyes) out of the subretinal space, despite albumin entry and without major osmolar shifts.

Topics: Animals; Blood-Retinal Barrier; Body Fluids; Disease Models, Animal; Electrophoresis, Polyacrylamide Gel; Fluorescein-5-isothiocyanate; Fluorophotometry; Iodates; Osmolar Concentration; Pigment Epithelium of Eye; Rabbits; Retinal Detachment; Serum Albumin; Serum Albumin, Bovine; Sodium Chloride

Small, experimental, non-rhegmatogenous retinal detachments (blebs) in rabbit eyes resorbed 50% more slowly when filled with autologous serum than with Hanks' solution. To study the fate of large molecules in the subretinal space, carboxyfluorescein and several sizes of FITC-dextrans were injected into blebs and their movement followed by fluorophotometry. Carboxyfluorescein diffused quickly into the vitreous and was gone from the space after 8 hr. FITC-dextran 10-S (smaller than albumin) also diffused readily into the vitreous and took about 30 hr to be eliminated from the subretinal space. The diffusion of FITC-dextran 70-S and 150-S (both larger than albumin) was markedly slower, and roughly 80% of the 150-S was still present in the subretinal space after 3 days. Since the subretinal fluid in all of these blebs resorbed within 10 hr, the physiologic mechanisms for fluid resorption and elimination of large substances appear to be independent. Damaging the RPE barrier with sodium iodate allowed even the larger FITC-dextrans to exit from the subretinal space.

Topics: Absorption; Animals; Dextrans; Diffusion; Fluorescein Angiography; Fluorescein-5-isothiocyanate; Fluoresceins; Iodates; Kinetics; Macromolecular Substances; Pigment Epithelium of Eye; Rabbits; Retinal Detachment; Sodium Chloride