Berdugo Marianne, Bejjani Riad A, Valamanesh Fatemeh, Savoldelli Michele, Jeanny Jean-Claude, Blanc Dominique, Ficheux Herve, Scherz Avigdor, Salomon Yoram, BenEzra David, Behar-Cohen Francine
Centre de Recherche des Cordeliers, Physiopathology of Ocular Diseases: Therapeutic Innovations, UMR S 872, Université Paris Descartes, Paris, France.
Invest Ophthalmol Vis Sci. 2008 Apr;49(4):1633-44. doi: 10.1167/iovs.07-0767.
To evaluate the photodynamic potential of a new hydrosoluble photosensitizer (WST-11, Stakel; Steba Biotech, Toussus-Le-Noble, France), for use in occlusion of normal choroidal vessels in the rabbit eye and CNV (choroidal neovascularization) in the rat eye.
Occlusive and nonocclusive parameters of Stakel and verteporfin photodynamic therapy (PDT) were investigated in pigmented rabbits. Eyes were followed by fluorescein angiography (FA) and histology at various intervals after PDT.
When occlusive parameters (fluence of 50 J/cm(2), 5 mg/kg drug dose and DLI [distance to light illumination] of 1 minute) were used, Stakel PDT was efficient immediately after treatment without associated structural damage of the RPE and retina overlying the treated choroid in the rabbit eye. Two days later, total occlusion of the choriocapillaries was seen in 100% of the treated eyes, along with accompanying histologic structural changes in the overlying retina. When the occlusive parameters (fluence, 100 J/cm2; drug dose, 12 mg/m2; and DLI, 5 minutes) of verteporfin PDT were used, occlusion of the choriocapillaries was observed in 89% of the treated eyes. Histology performed immediately after treatment demonstrated structural damage of the overlying retina and RPE layer. Weaker, nonocclusive Stakel PDT parameters (25 J/cm2, 5 mg/kg, and DLI of 10 minutes) did not induce choriocapillary occlusion or retinal lesions on FA or histology. Weaker, nonocclusive verteporfin PDT parameters (10 J/cm2, 0.2 mg/kg, and DLI of 5 minutes) did not induce choriocapillary occlusion. However, histology of these eyes showed the presence of damage in the retinal and choroidal tissues. Moreover, preliminary results indicate that selective CNV occlusion can be achieved with Stakel PDT in the rat eye.
Unlike verteporfin PDT, Stakel PDT does not cause direct damage to the RPE cell layer or retina. These observations indicate that Stakel PDT may have a high potential for beneficial therapeutic outcomes in treatment of AMD.
评估一种新型水溶性光敏剂（WST - 11，Stakel；法国图叙莱诺布尔市的Steba Biotech公司）在兔眼中阻塞正常脉络膜血管以及在大鼠眼中阻塞脉络膜新生血管（CNV）的光动力潜力。
在色素沉着兔中研究了Stakel和维替泊芬光动力疗法（PDT）的阻塞性和非阻塞性参数。在PDT后的不同时间间隔，通过荧光素血管造影（FA）和组织学对眼睛进行观察。
当采用阻塞性参数（能量密度为50 J/cm²、药物剂量为5 mg/kg以及光照距离[DLI]为1分钟）时，Stakel PDT在治疗后即刻有效，且兔眼中治疗的脉络膜上方的视网膜色素上皮（RPE）和视网膜未出现相关结构损伤。两天后，100%的治疗眼可见脉络膜毛细血管完全阻塞，同时上方视网膜伴有组织学结构变化。当采用维替泊芬PDT的阻塞性参数（能量密度为100 J/cm²、药物剂量为12 mg/m²以及DLI为5分钟）时，89%的治疗眼观察到脉络膜毛细血管阻塞。治疗后即刻进行的组织学检查显示上方视网膜和RPE层存在结构损伤。较弱的非阻塞性Stakel PDT参数（25 J/cm²、5 mg/kg以及DLI为10分钟）在FA或组织学上未诱导脉络膜毛细血管阻塞或视网膜病变。较弱的非阻塞性维替泊芬PDT参数（10 J/cm²、0.2 mg/kg以及DLI为5分钟）未诱导脉络膜毛细血管阻塞。然而，这些眼睛的组织学检查显示视网膜和脉络膜组织存在损伤。此外，初步结果表明，Stakel PDT可在大鼠眼中实现选择性CNV阻塞。
与维替泊芬PDT不同，Stakel PDT不会对RPE细胞层或视网膜造成直接损伤。这些观察结果表明，Stakel PDT在治疗年龄相关性黄斑变性（AMD）方面可能具有很高的有益治疗效果潜力。
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