To determine if intravitreal triamcinolone acetonide (TAAC) inhibits experimental choroidal neovascular membranes induced by laser trauma in a rat model. Methods: Nineteen anesthetized male Brown Norway rats received a series of 8 krypton red laser lesions per eye (647 nm, 0.05 seconds, 50 µm, and 150 mW in 17 rats, and 200 mW in 2 rats). One eye received an intravitreal injection of triamcinolone acetonide (20 µL, 0.8 mg) and the other eye received an injection of isotonic sodium chloride solution. Fundus and fluorescein angiography examinations occurred just before euthanasia and tissue processing for histopathology on day(s) 0
The use of steroids to treat a number of retinal diseases is gaining wide spread acceptance. The apparent short-term success must be balanced by the fact that the long-term safety and efficacy have yet to be determined for any of these approaches. A number of large randomized prospective clinical trials of steroid compounds and new delivery systems are currently under way for AMD, diabetic retinopathy, uveitis, and other retinovascular diseases, and hopefully these studies will provide guidance about the use of these new modalities.
Aim: To determine if intravitreal microimplants containing triamcinolone acetonide (TAAC) inhibit experimental fibrovascular proliferation (FVP) induced by laser trauma in a rat as a model of choroidal neovascular membranes (CNVMs). Methods: 20 anaesthetised male Brown Norway rats received a series of eight krypton red laser lesions per eye (647 nm, 0.05 s, 50 µm, 150 mW). Three types of sterilised TAAC microimplant designs were evaluated: implant A consisting of 8.62% TAAC/20% polyvinyl alcohol (PVA) matrix (by dry weight); implant B consisting of 3.62% TAAC/20% PVA matrix; and implant C consisting of a dual 8.62% TAAC/20% PVA matrix design combined with a central core (0.5 mm) of compressed TAAC to extend the implant release time. For each animal studied, one eye received one of the three aforementioned TAAC implant designs, while the fellow eye received a control implant consisting of PVA but without TAAC. The animals were sacrificed at day 35 and ocular tissues were processed for histological analysis. Serial histological specimens were methodically assessed in a masked fashion to analyse each laser lesion for the presence or absence of FVP; maximum FVP thickness for each lesion was measured from the choriocapillaris. Results: All three types of TAAC implants inhibited FVP relative to controls in a statistically significant fashion. In the eyes that received implant A (n = 8), the mean thickness of the recovered lesions (n = 36) measured 32 (SD 22) µm, compared to 52 (30) µm (p <0.005) for the recovered lesions (n = 40) from the fellow control eyes. In the eyes that received implant B (n = 6), the mean thickness of the recovered lesions (n = 31) measured 28 (15) µm, compared to 50 (29) µm (p <0.001) for the lesions (n = 19) recovered from the fellow control eyes. In the eyes that received implant C (n = 6), the mean thickness of the recovered lesions (n = 21) measured 39 (24) µm, compared to 65 (30) µm (p <0.001) for the lesions (n = 39) recovered from the fellow control eyes. Conclusions: All three of the tested TAAC microimplant designs produced potent inhibition of FVP in a rat model of CNVMs. There were no differences in inhibition of FVP between the three different types of implants evaluated. This study provides evidence that: (1) corroborates previous investigations that propose TAAC as a potential treatment for CNVMs in humans, and (2) demonstrates TAAC can be effectively delivered via long acting sustained release intraocular microimplants. It should be noted, however, that the FVP observed in this rat laser trauma may not reflect the CNVM observed in human with exudative age related macular degeneration (AMD).A ntiangiogenic steroids have been proposed as treatment for the choroidal neovascular membranes (CNVMs) that cause visual loss in exudative age related macular degeneration (AMD).1-3 Although there are no direct animal models of AMD related CNVMs, there are several animal models in which laser trauma induces fibrovascular proliferation (FVP) arising from the choroid as a model of CNVM. The ra...
The cholinergic identity of retinal starburst amacrine neurons is well established, but recent evidence suggests that these cells are GABAergic as well. Confirmation of this dual transmitter function requires the demonstration of glutamate decarboxylase (GAD), the biosynthetic enzyme for GABA, within starburst cells. The current work was undertaken to determine whether rabbit retinal starburst amacrine neurons contain either of the two known isoforms of GAD. To do this, we have examined the localization of the following: (1) the 65-kDa isoform of GAD; (2) the 67-kDa isoform of GAD; (3) choline acetyltransferase; and (4) the fluorescent dye DAPI, a marker for cholinergic amacrine cells. In addition, we labeled displaced starburst neurons directly, by injecting them with Lucifer Yellow in vitro. Four strata within the inner plexiform layer contained immunoreactive GAD65. A non-GAD65-immunoreactive zone separated the two innermost strata (G3 and G4); this zone contained (1) the dendrites of individual Lucifer Yellow-injected, displaced starburst amacrine cells; (2) dendrites immunoreactive for choline acetyltransferase; and (3) processes of DAPI-labeled amacrine cells. Immunoreactive GAD67 appeared in the same strata that contained GAD65, and in at least two additional strata, one of which lay at precisely the same depth as the proximal cholinergic stratum. In addition, the somas of displaced starburst cells were strongly immunoreactive for GAD67, but not for GAD65. These results demonstrate (1) that displaced starburst amacrine cells contain the 67-kDa isoform of GAD, but not the 65-kDa isoform; and (2) that the dendrites of starburst (67-kDa GAD) amacrines, and the dendrites of 65-kDa-GAD-containing amacrines, occupy different strata within the inner plexiform layer. Thus, displaced starburst cells do contain GAD, and can, presumably, manufacture GABA. The reasons for their preferential use of the 67-kDa GAD isoform remain to be elucidated.
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